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INTERLEUKIN 22
LATEST LITERATURE
1: Inflammatory bowel diseases, 2010 Sep 7,
DMBT1 is a novel gene induced by IL-22 in ulcerative colitis.
[Abstract]BACKGROUND:: Interleukin (IL)-22 is a recently identified cytokine that is suggested to play pivotal roles in various inflammatory diseases. Although the IL-22 receptor 1 (IL-22R1) is restrictively expressed in epithelial cells in the colon, the role of IL-22 in colonic diseases still remains unclear. In this study microarray analyses revealed that deleted in malignant brain tumors 1 (DMBT1) is a novel upregulated gene in IL-22-stimulated colon cancer cells. Therefore, we investigated the involvement of DMBT1 and IL-22 in ulcerative colitis (UC) tissues and examined the mechanism regulating the expression of DMBT1 in response to IL-22 stimulation. METHODS:: Changes of gene expression in IL-22-stimulated SW403 cells were investigated by microarray analyses. The effects of IL-22 on DMBT1 expression were examined in SW403 cells using a small interfering RNA (si)RNA for STAT3 or inhibitors for MEK, PI3K, and nuclear factor kappa B (NF-kappaB). The element responsible for IL-22-induced DMBT1 promoter activation was determined by a promoter deletion and electrophoretic mobility shift assay (EMSA). Expression of IL-22, IL-22R1, and DMBT1 in UC tissues was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS:: IL-22 treatment enhanced the expression of DMBT1 through STAT3 tyrosine phosphorylation and NF-kappaB activation in colon cancer cells. The IL-22-responsive element was located between -187 and -179 in the DMBT1 promoter region. In the UC mucosa the levels of DMBT1 and IL-22 mRNA expression were significantly enhanced and positively correlated, the numbers of IL-22-positive lymphocytes were increased, and the expression of IL-22R1 and DMBT1 was enhanced in the inflamed epithelium. CONCLUSIONS:: The IL-22/DMBT1 axis may play a pivotal role in the pathophysiology of UC. (Inflamm Bowel Dis 2010;).
2: European journal of immunology, 2010 Sep, 40(9)
IL-22-producing CD4(+) T cells: Middle-men between the immune system and its environment.
[Abstract]CD4(+) Th cell populations such as Th1, Th2, Th17 and regulatory T cells regulate immune responses by inducing (or inhibiting) proliferation, differentiation and activation of other immune cells. Recent findings have expanded the universe of CD4(+) T-cell subsets by identifying a cell population dedicated to the production of the cytokine IL-22. These so-called Th22 cells may mediate interactions of the immune system with stromal cells. Th22 cells have so far only been observed in humans and are present in inflamed tissues in some skin diseases and evidence suggests that these cells may play a role in the disease process. It is therefore of importance to learn the mechanisms of regulation of development and function of these cells. A paper in the current issue of the European Journal of Immunology indicates that the ligand-dependent transcription factor aryl hydrocarbon receptor is important for regulating IL-22 production of this new class of human Th cells.
3: Journal of immunology (Baltimore, Md. : 1950), 2010 Aug 27, 67(17)
Immature NK Cells, Capable of Producing IL-22, Are Present in Human Uterine Mucosa.
[Abstract]NK cells are the dominant population of immune cells in the endometrium in the secretory phase of the menstrual cycle and in the decidua in early pregnancy. The possibility that this is a site of NK cell development is of particular interest because of the cyclical death and regeneration of the NK population during the menstrual cycle. To investigate this, we searched for NK developmental stages 1-4, based on expression of CD34, CD117, and CD94. In this study, we report that a heterogeneous population of stage 3 NK precursor (CD34(-)CD117(+)CD94(-)) and mature stage 4 NK (CD34(-)CD117(-/+)CD94(+)) cells, but not multipotent stages 1 and 2 (CD34(+)), are present in the uterine mucosa. Cells within the uterine stage 3 population are able to give rise to mature stage 4-like cells in vitro but also produce IL-22 and express RORC and LTA. We also found stage 3 cells with NK progenitor potential in peripheral blood. We propose that stage 3 cells are recruited from the blood to the uterus and mature in the uterine microenvironment to become distinctive uterine NK cells. IL-22 producers in this population might have a physiological role in this specialist mucosa dedicated to reproduction.
4: European journal of immunology, 2010 Jul 13, 185(2)
Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells.
[Abstract]Ligands of the aryl hydrocarbon receptor (AHR), a transcription factor mediating the effects of dioxin, favor Th17 differentiation and exacerbate autoimmunity in mice. We investigated how AHR ligands affected human T-cell polarization. We found that the high affinity and stable AHR-ligand dioxin as well as the natural AHR-ligand 6-formylinolo[3,2-b] carbazole induced the downstream AHR-target cytochrome P450A1, and without affecting IFN-gamma, they enhanced IL-22 while simultaneously decreasing IL-17A production by CD4(+) T cells. The specific AHR-inhibitor CH-223191 abolished these effects. Furthermore, blockade of IL-23 and IL-1, important for Th17 expansion, profoundly decreased IL-17A but not IL-22 production. AHR agonists reduced the expression of the Th17 master transcription factor retinoic acid-related orphan receptor C (RORC), without affecting T-bet, GATA-3 and Foxp3. They also decreased the expression of the IL-23 receptor. Importantly, AHR-ligation did not only decrease the number of Th17 cells but also primed na?ve CD4(+) T cells to produce IL-22 without IL-17 and IFN-gamma. Furthermore, IL-22 single producers did not express CD161, which distinguished them from the CD161(+) Th17 cells. Hence, our data provide compelling evidence that AHR activation participates in shaping human CD4(+) T-cell polarization favoring the emergence of a distinct subset of IL-22-producing cells that are independent from the Th17 lineage.
5: Iranian journal of allergy, asthma, and immunology, 2010 Jun, 9(2)
Evaluation of the Effect of IL-22 on Human Cord Blood CD4+ T Cells.
[Abstract]IL-22 is a member of IL-10 cytokine family which is believed to play an important role in inflammatory responses. IL-22 has similarities with IL-10 including conserved sequences with IL-10. IL-22 receptor is also comprised of two chains known as L-22R1 and L-10R2; supporting the speculation that the two cytokines may have similar effects. The aim of this study was to shed some light on the biological activity of IL-22 upon the cord blood CD4+CD25- T cells. In this research, cord blood T CD4+CD25- cells were cultured in presence of anti CD2/CD3/CD28 coated beads, IL-2 and IL-22 for two weeks at 37 degrees C and 5% CO2. Flow cytometry analysis showed that IL-22 has no effect upon CD25 and Foxp3 expression. Also, the results indicated that IL-22 is not involved in CD4+ T cell proliferation. Moreover, the results of suppression assay did not show any suppression effect on the cultured T cells. Thus, it seems that umbilical cord blood T cells probably do not express IL-22R1 on their surface.
6: Immunity, 2010 Jun 25, 32(6)
Interleukin-1beta Selectively Expands and Sustains Interleukin-22(+) Immature Human Natural Killer Cells in Secondary Lymphoid Tissue.
[Abstract]Among human natural killer (NK) cell intermediates in secondary lymphoid tissue (SLT), stage 3 CD34(-)CD117(+)CD161(+)CD94(-) immature NK (iNK) cells uniquely express aryl hydrocarbon receptor (AHR) and interleukin-22 (IL-22), supporting a role in mucosal immunity. The mechanisms controlling proliferation and differentiation of these cells are unknown. Here we demonstrate that the IL-1 receptor IL-1R1 was selectively expressed by a subpopulation of iNK cells that localized proximal to IL-1beta-producing conventional dendritic cells (cDCs) within SLT. IL-1R1(hi) iNK cells required continuous exposure to IL-1beta to retain AHR and IL-22 expression, and they proliferate in direct response to cDC-derived IL-15 and IL-1beta. In the absence of IL-1beta, a substantially greater fraction of IL-1R1(hi) iNK cells differentiated to stage 4 NK cells and acquired the ability to kill and secrete IFN-gamma. Thus, cDC-derived IL-1beta preserves and expands IL-1R1(hi)IL-22(+)AHR(+) iNK cells, potentially influencing human mucosal innate immunity during infection.
7: Journal of virology, 2010 May 26,
IL-22 production by pulmonary natural killer cells and the potential role of IL-22 during primary influenza infection.
[Abstract]We set out to test the hypothesis that IL-22, a cytokine crucial for epithelial cell homeostasis and recovery from tissue injury, would be protective during influenza virus infection. Recent studies have identified phenotypically and functionally unique intestinal NK cells capable of producing the cytokine IL-22. Unlike gut NK cells that produce IL-22, the surface phenotypes of the lung NK cells were similar to spleen NK cells and characteristically mature. With mitogen stimulation, both single and double IL-22 and IFN-gamma lung producing NK cells were detected. However, only the IL-22+IFN-gamma- lung NK subset was observed after stimulation with IL-23. IL-23 receptor (IL-23R) blocking dramatically inhibited IL-22 production, but not IFN-gamma. Further, we found NK1.1+ or CD27- lung NK cells were the primary sources of IL-22. After influenza virus infection, lung NK cells were quickly activated to produce both IFN-gamma and IL-22, and had increased cytotoxic potential. The level of IL-22 in the lung tissue declined shortly after infection, gradually returning to baseline after virus clearance, although the IL-22 gene expression was maintained. Further, depletion of NK cells with or without influenza infection reduced the protein level of IL-22 in the lung. Anti-IL-22 neutralization in vivo did not dramatically affect weight loss and survival after virus clearance. Unexpectedly, anti-IL-22 treated mice had reduced virus titers. Our data suggest that during primary respiratory viral infection, IL-22 seems to play marginal role for protection, indicating a differential requirement of this cytokine for bacterial and viral infections.
8: The Journal of experimental medicine, 2010 May 24,
Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A.
[Abstract]IL-22 has both proinflammatory and tissue-protective properties depending on the context in which it is expressed. However, the factors that influence the functional outcomes of IL-22 expression remain poorly defined. We demonstrate that after administration of a high dose of bleomycin that induces acute tissue damage and airway inflammation and is lethal to wild-type (WT) mice, Th17 cell-derived IL-22 and IL-17A are expressed in the lung. Bleomycin-induced disease was ameliorated in Il22(-/-) mice or after anti-IL-22 monoclonal antibody (mAb) treatment of WT mice, indicating a proinflammatory/pathological role for IL-22 in airway inflammation. However, despite increased bleomycin-induced IL-22 production, Il17a(-/-) mice were protected from airway inflammation, suggesting that IL-17A may regulate the expression and/or proinflammatory properties of IL-22. Consistent with this, IL-17A inhibited IL-22 production by Th17 cells, and exogenous administration of IL-22 could only promote airway inflammation in vivo by acting in synergy with IL-17A. Anti-IL-22 mAb was delivered to Il17a(-/-) mice and was found to exacerbate bleomycin-induced airway inflammation, indicating that IL-22 is tissue protective in the absence of IL-17A. Finally, in an in vitro culture system, IL-22 administration protected airway epithelial cells from bleomycin-induced apoptosis, and this protection was reversed after coadministration of IL-17A. These data identify that IL-17A can regulate the expression, proinflammatory properties, and tissue-protective functions of IL-22, and indicate that the presence or absence of IL-17A governs the proinflammatory versus tissue-protective properties of IL-22 in a model of airway damage and inflammation.
9: Journal of immunology (Baltimore, Md. : 1950), 2010 May 14,
Cytokine Requirements for the Differentiation and Expansion of IL-17A- and IL-22-Producing Human V{gamma}2V{delta}2 T Cells.
[Abstract]Human gammadelta T cells expressing the Vgamma2Vdelta2 TCR play important roles in immune responses to microbial pathogens by monitoring prenyl pyrophosphate isoprenoid metabolites. Most adult Vgamma2Vdelta2 cells are memory cytotoxic cells that produce IFN-gamma. Recently, murine gammadelta T cells were found to be major sources of IL-17A in antimicrobial and autoimmune responses. To determine if primate gammadelta T cells play similar roles, we characterized IL-17A and IL-22 production by Vgamma2Vdelta2 cells. IL-17A-producing memory Vgamma2Vdelta2 cells exist at low but significant frequencies in adult humans (1:2762 T cells) and at even higher frequencies in adult rhesus macaques. Higher levels of Vgamma2Vdelta2 cells produce IL-22 (1:1864 T cells), although few produce both IL-17A and IL-22. Unlike adult humans, in whom many IL-17A(+) Vgamma2Vdelta2 cells also produce IFN-gamma (Tgammadelta1/17), the majority of adult macaques IL-17A(+) Vdelta2 cells (Tgammadelta17) do not produce IFN-gamma. To define the cytokine requirements for Tgammadelta17 cells, we stimulated human neonatal Vgamma2Vdelta2 cells with the bacterial Ag, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, and various cytokines and mAbs in vitro. We find that IL-6, IL-1beta, and TGF-beta are required to generate Tgammadelta17 cells in neonates, whereas Tgammadelta1/17 cells additionally required IL-23. In adults, memory Tgammadelta1/17 and Tgammadelta17 cells required IL-23, IL-1beta, and TGF-beta, but not IL-6. IL-22-producing cells showed similar requirements. Both neonatal and adult IL-17A(+) Vgamma2Vdelta2 cells expressed elevated levels of retinoid-related orphan receptor gammat. Our data suggest that, like Th17 alphabeta T cells, Vgamma2Vdelta2 T cells can be polarized into Tgammadelta17 and Tgammadelta1/17 populations with distinct cytokine requirements for their initial polarization and later maintenance.
10: American journal of respiratory cell and molecular biology, 2010 May 12,
Protective Properties of Inhaled IL-22 in a Model of Ventilator-induced Lung Injury.
[Abstract]High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). Interleukin (IL)-22 has both immunoregulatory and tissue protective properties. Functional IL-22 receptor expression is restricted to non-leukocytic cells such as alveolar epithelial cells. When applied via inhalation, IL-22 reaches the pulmonary system directly and in high concentrations and may protect alveolar epithelial cells against cellular stress and biotrauma associated with VILI. In A549 lung epithelial cells IL-22 was able to induce rapid STAT3 phosphorylation/activation and hereon mediated stable SOCS3 expression detectable even 24h after onset of stimulation. In a rat model of VILI the prophylactic inhalation of IL-22 prior to induction of VILI (pmax = 45 cmH2O) protected the lung against pulmonary disintegration and edema. IL-22 reduced VILI-associated biotrauma (i.e. pulmonary concentrations of MIP-2, IL-6 and MMP9) and mediated pulmonary STAT3/SOCS3 activation. In addition, despite a short observation period of 4 hours, inhaled IL-22 resulted in an improved survival of the rats. These data support the hypothesis that IL-22, likely via activation of STAT3 and downstream genes (e.g. SOCS3), is able to protect against cell stretch and pulmonary baro-/biotrauma by enhancing epithelial cell resistibility.
11: Cellular and molecular life sciences : CMLS, 2010 May 8,
Structure and function of interleukin-22 and other members of the interleukin-10 family.
[Abstract]The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-lambdas (IL-28A, IL-28B, and IL-29). The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.
12: Journal of hepatology, 2010 Apr 21, 50(2)
Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22.
[Abstract]BACKGROUND & AIMS: Interleukin-22 (IL-22) is a Th17-related cytokine within the IL-10 family and plays an important role in host defense and inflammatory responses in orchestration with other Th17 cytokines. IL-22 exerts its functions in non-immune cells as its functional receptor IL-22R1 is restricted in peripheral tissues but not in immune cells. It was recently found that IL-22 serves as a protective molecule to counteract the destructive nature of the T cell-mediated immune response to liver damage. However, it is currently unknown whether IL-22 has an effect on lipid metabolism in the liver. METHODS: In this study, we demonstrate that IL-22 alleviates hepatic steatosis induced by high fat diet (HFD). RESULTS: Administration of recombinant murine IL-22 (rmIL-22) was able to stimulate STAT3 phosphorylation in HepG2 cells and mouse liver. The activation of STAT3 by rmIL-22 was reduced by the over-expression of a dominant negative IL-22R1. Within hours after rmIL-22 treatment, the expression of lipogenesis-related genes including critical transcription factors and enzymes for lipid synthesis in the liver was significantly down-regulated. The levels of triglyceride and cholesterol in the liver were significantly reduced by long-term treatment of rmIL-22 in C57BL/6 and ob/ob mice fed with HFD. The HFD-induced increases of ALT and AST in ob/ob mice were ameliorated by rmIL-22 treatment. In addition, the expression of fatty acid synthase and TNF-alpha in the liver was decreased by long-term rmIL-22 administration. CONCLUSIONS: Collectively, these data indicate that IL-22, in addition to its known functions in host defense and inflammation, has a protective role in HFD-induced hepatic steatosis via its regulation on lipid metabolism in the liver.
13: Journal of dermatological science, 2010 Apr 3, 184(8)
Serum IL-22 correlates with psoriatic severity and serum IL-6 correlates with susceptibility to phototherapy.
[Abstract]IL-22 is a member of the IL-10 cytokine family and signals through a heterodimeric receptor composed of the common IL-10R2 subunit and the IL-22R subunit. IL-10 and IL-22 both activate the STAT3 signaling pathway; however, in contrast to IL-10, relatively little is known about IL-22 in the host response to infection. In this study, using IL-22(-/-) mice, neutralizing Abs to IL-22, or both, we show that IL-22 is dispensable for the development of immunity to the opportunistic pathogens Toxoplasma gondii and Mycobacterium avium when administered via the i.p. or i.v. route, respectively. IL-22 also played little to no role in aerosol infections with Mycobacterium tuberculosis and in granuloma formation and hepatic fibrosis following chronic percutaneous infections with the helminth parasite Schistosoma mansoni. A marked pathogenic role for IL-22 was, however, identified in toxoplasmosis when infections were established by the natural oral route. Anti-IL-22 Ab-treated mice developed significantly less intestinal pathology than control Ab-treated mice even though both groups displayed similar parasite burdens. The decreased gut pathology was associated with reduced IL-17A, IL-17F, TNF-alpha, and IFN-gamma expression. In contrast to the prior observations of IL-22 protective effects in the gut, these distinct findings with oral T. gondii infection demonstrate that IL-22 also has the potential to contribute to pathogenic inflammation in the intestine. The IL-22 pathway has emerged as a possible target for control of inflammation in certain autoimmune diseases. Our findings suggest that few if any infectious complications would be expected with the suppression of IL-22 signaling.
14: Cancer causes & control : CCC, 2010 Mar 26, 50(3)
Interleukin-22 genetic polymorphisms and risk of colon cancer.
[Abstract]Interleukin-22 (IL-22) is a member of the IL-10 family of anti-inflammatory cytokines that mediates epithelial immunity. IL-22 expression is enhanced in inflamed colon mucosa in individuals with inflammatory bowel disease. We carried out an association study to examine the hypothesis that common variation in the IL-22 gene is associated with risk of colon cancer. Seven tagging SNPs were genotyped in 561 colon cancer cases and 722 population controls. Information on lifestyle risk factors was collected via a self-administered questionnaire. The rs1179251 SNP conferred an estimated odds ratio (OR) of 1.46 (95% CI = 1.04-2.05) and 2.10 (95% CI = 0.66-6.66), respectively, for those heterozygous and homozygous for the G variant (p (additive) = 0.013) after adjustment for age, gender, and race; the OR assuming a dominant model was 1.50 (95% CI = 1.05-2.08, p (dominant) = 0.016). No other SNP was statistically significantly associated with colon cancer risk. Haplotype analysis found that one haplotype containing the rs1179251 G allele gave an estimated 52% increase in risk of colon cancer for individuals with at least one copy (OR = 1.52, 95% CI = 1.12-2.06, p = 0.0073). Our findings suggest that the rs1179251 SNP in IL-22 is associated with risk of colon cancer.
15: Journal of immunology (Baltimore, Md. : 1950), 2010 Mar 24, 50(3)
Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1{alpha}, and TNF-{alpha} Recapitulates Some Features of Psoriasis.
[Abstract]Keratinocytes play a crucial role in the regulation of skin inflammation, responding to environmental and immune cells stimuli. They produce soluble factors that can act in an autocrine or paracrine manner on immune cells or directly on aggressors. A screening of the activities of 36 cytokines on keratinocyte gene expression identified IL-17A, IL-22, oncostatin M, TNF-alpha, and IL-1alpha as potent cytokines in inducing cutaneous inflammation. These five proinflammatory cytokines synergistically increased production of CXCL8 and beta-defensin 2 (BD2). In addition, ex vivo studies on human skin explants demonstrated upregulation of BD2, S100A7, and CXCL8 expression in response to the same combination of cytokines. In vivo intradermal injection of these five cytokines in mouse increased CXCL1, CXCL2, CXCL3, S100A9, and BD3 expression, associated with neutrophil infiltration. We confirmed and extended this synergistic effect using quantitative real-time PCR analysis and observed increased expression of nine chemokines and 12 antimicrobial peptides. Production of CXCL, CXCL5, and CXCL8 by keratinocytes stimulated in the presence of this cytokine combination was associated with increased neutrophil chemotactic activity. Similarly, high production of BD2, BD3, and S100A7 was associated with an increased antimicrobial activity. Finally, the transcriptional profile observed in this in vitro model of inflammatory keratinocytes correlated with the one of lesional psoriatic skin. Our results demonstrate the important potentiating activities of IL-17A, IL-22, oncostatin M, TNF-alpha, and IL-1alpha on keratinocytes. This is particularly interesting in the context of psoriasis where these cytokines are overexpressed and could synergize to play an important role in upregulation of chemokines and antimicrobial peptides production.
16: Proceedings of the National Academy of Sciences of the United States of America, 2010 Mar 15, 50(3)
Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor.
[Abstract]CD4(+) helper T (Th) cells differentiate toward distinct effector cell lineages characterized by their distinct cytokine expression patterns and functions. Multiple Th cell populations secrete IL-22 that contributes to both protective and pathological inflammatory responses. Although the differentiation of IL-22-producing Th cells is controlled by the aryl hydrocarbon receptor (AhR), little is known about the regulatory mechanisms inducing physiological stimulators for AhR. Here, we show that Notch signaling enhances IL-22 production by CD4(+) T cells by a mechanism involving AhR stimulation. Notch-mediated stimulation of CD4(+) T cells increased the production of IL-22 even in the absence of STAT3. CD4(+) T cells from RBP-J-deficient mice had little ability to produce IL-22 through T cell receptor-mediated stimulation. RBP-J-deficient mice were highly susceptible to the detrimental immunopathology associated with ConA-induced hepatitis with little IL-22 production by CD4(+) T cells. Exogenous IL-22 protected RBP-J-deficient mice from ConA-induced hepatitis. Notch signaling promoted production of endogenous stimulators for AhR, which further augmented IL-22 secretion. Our studies identify a Notch-AhR axis that regulates IL-22 expression and fine-tunes immune system control of inflammatory responses.
17: Inflammatory bowel diseases, 2010 Mar 10, 50(3)
Colonic epithelial upregulation of interleukin 22 (IL-22) in patients with ulcerative colitis.
[Abstract]Chronic heart failure (CHF) is a complex and heterogeneous clinical syndrome and because of its rising incidence and prevalence, it can be considered a global epidemic. Interleukin (IL)-22 is a pro-inflammatory cytokine, belonging to the IL-10 family. Forty-seven consecutive older patients, hospitalized with an admitting diagnosis of CHF at the Geriatric Medicine Unit (University of Messina, Italy), from 01/01/06 to 30/06/06, were enrolled in the study. Serum concentrations of IL-22 were measured by a quantitative enzyme immunoassay technique. IL-22 levels in all CHF patients were significantly higher than those in controls, in particular, only the II and III NYHA class had IL-22 values significantly higher than the controls, whereas there was no difference between the IL-22 levels of NYHA class IV and the controls. The reason may be the declining immune function in CHF older patients, in fact we can hypothesize that the fall in IL-22 levels, with the progression of NYHA class, is due to the reduced ability in CHF patients to respond to infections, as IL-22 has anti-microbial properties. We detected different outcomes correlated to different IL-22 levels, and the Kaplan-Meier curves suggest a trend.
18: Shock (Augusta, Ga.), 2010 Mar 9, 7(1)
INTERLEUKIN-22 DETECTED IN PATIENTS WITH ABDOMINAL SEPSIS.
[Abstract]Interleukin (IL)-22 is a Th17-like cytokine known to specifically activate epithelial cells thereby strengthening immune defence at host/environment interfaces. Animal studies suggest that IL-22 may play a crucial role in clinical sepsis. However, little is known about IL-22 in sepsis patients. In a single-center University Hospital setting serum IL-22 levels were assessed in sixteen patients with the diagnosis of abdominal sepsis, sixteen patients that have undergone elective major abdominal surgery without the diagnosis of sepsis, and twenty-one healthy volunteers. In accord with current knowledge, we observed enhanced levels of IL-6 and IL-10 in serum specimens of sepsis patients as compared to surgical control patients. Here, we report for the first time on modest but significant elevation of serum IL-22 detectable in abdominal sepsis patients (p < 0.001). Median serum concentrations of IL-22 were 111.8 pg/ml, 3.4 or 2.0 pg/ml, and 9.3 pg/ml for abdominal sepsis patients, surgical control patients (pre- or post-surgery), and healthy volunteers, respectively. IL-22 produced in the course of abdominal sepsis may contribute to host defence and stabilization of mucosal barrier functions under conditions of systemic infection.
19: Journal of immunology (Baltimore, Md. : 1950), 2010 Mar 10, 50(3)
Redundant and Pathogenic Roles for IL-22 in Mycobacterial, Protozoan, and Helminth Infections.
[Abstract]IL-22 is a member of the IL-10 cytokine family and signals through a heterodimeric receptor composed of the common IL-10R2 subunit and the IL-22R subunit. IL-10 and IL-22 both activate the STAT3 signaling pathway; however, in contrast to IL-10, relatively little is known about IL-22 in the host response to infection. In this study, using IL-22(-/-) mice, neutralizing Abs to IL-22, or both, we show that IL-22 is dispensable for the development of immunity to the opportunistic pathogens Toxoplasma gondii and Mycobacterium avium when administered via the i.p. or i.v. route, respectively. IL-22 also played little to no role in aerosol infections with Mycobacterium tuberculosis and in granuloma formation and hepatic fibrosis following chronic percutaneous infections with the helminth parasite Schistosoma mansoni. A marked pathogenic role for IL-22 was, however, identified in toxoplasmosis when infections were established by the natural oral route. Anti-IL-22 Ab-treated mice developed significantly less intestinal pathology than control Ab-treated mice even though both groups displayed similar parasite burdens. The decreased gut pathology was associated with reduced IL-17A, IL-17F, TNF-alpha, and IFN-gamma expression. In contrast to the prior observations of IL-22 protective effects in the gut, these distinct findings with oral T. gondii infection demonstrate that IL-22 also has the potential to contribute to pathogenic inflammation in the intestine. The IL-22 pathway has emerged as a possible target for control of inflammation in certain autoimmune diseases. Our findings suggest that few if any infectious complications would be expected with the suppression of IL-22 signaling.
20: The Journal of experimental medicine, 2010 Feb 8, 184(4)
Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells.
[Abstract]Lymphoid tissue inducer (LTi) cells are required for lymph node formation during fetal development, and recent evidence implies a role in mucosal immunity in the adult. LTi cells share some phenotypic features of conventional natural killer (NK; cNK) cells; however, little is known to date about the relationship between these two cell types. We show that lineage(-) (Lin(-)) CD127(+)RORC(+) LTi-like cells in human tonsil are precursors to CD56(+)CD127(+)RORC(+)NKp46(+) cells, which together comprise a stable RORC(+) lineage. We find that LTi-like cells and their CD56(+) progeny can be expanded and cloned ex vivo without loss of function and without conversion into cNK cells. Clonal analysis reveals heterogeneity of cytokine production within the CD127(+) LTi-like population. Furthermore, we identify within the tonsil a cNK precursor population that is characterized as Lin(-)CD117(+)CD161(+)CD127(-) cells. Overall, we propose that CD127(+)RORC(+) cells, although they share some characteristics with cNK cells, represent a functionally and developmentally distinct lineage.
21: Seminars in immunopathology, 2010 Feb 2, 184(4)
Biology of interleukin-22.
[Abstract]Interleukin (IL)-22 is a member of the IL-10 family of cytokines and represents an important effector molecule of activated Th22, Th1, and Th17 cells, as well as Tc-cell subsets, gammadelta T cells, natural killer (NK), and NKT cells. IL-22 mediates its effects via a heterodimeric transmembrane receptor complex consisting of IL-22R1 and IL-10R2 and subsequent Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathways including Jak1, Tyk2, and STAT3. Whereas in some aspects, IL-22 acts synergistically with tumor necrosis factor-alpha, IL-1beta, or IL-17, most functions of IL-22 are unique. Importantly, IL-22 does not serve the communication between immune cells. It mainly acts on epithelial cells and hepatocytes, where it favors the antimicrobial defense, regeneration, and protection against damage and induces acute phase reactants and some chemokines. This chapter illuminates in detail the properties of IL-22 with respect to its gene, protein structure, cellular sources, receptors, target cells, biological effects, and, finally, its role in chronic inflammatory diseases, tumors, and infection.
22: The Journal of experimental medicine, 2010 Feb 1, 451(1-2)
Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I.
[Abstract]Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.