Infection-induced IL-10 and JAK-STAT

Carey, Alison J.; Tan, CK; Ulett, Glen C.

doi:10.4161/jkst.19918

Cited by 58 publications

(41 citation statements)

References 107 publications

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“…Binding of IL-10 to the extracellular domain of the IL-10 receptor activates phosphorylation of the receptor-associated Janus kinase 1 (JAK1), tyrosine kinase 2 (Tyk2), and specific tyrosine residues on the intracellular domain of the IL-10 receptor, which binds STAT3, which then induces the interleukin-1 receptor antagonist (IL-1RA). IL-1RA binds to IL-1R to prevent IL-1␤ activation (42). In the absence of IL-10, IL-1RA activity is blocked, which results in elevation of the IL-1␤ level (22,43).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

et al. 2015

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e Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses against Chlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydia immunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates in Chlamydia-infected wild-type (WT) and IL-10-knockout (IL-10 ؊/؊ ) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1␤ production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection of Chlamydia-exposed dendritic cells (DCs) from WT and IL-10 ؊/؊ mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10 ؊/؊ mice were protected from tubal pathologies and infertility, whereas WT (IL-10 ؉/؉ ) mice were not. Chlamydia-pulsed IL-10 ؊/؊ DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1␤ production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10 ؊/؊ DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca 2؉ levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL-10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation against Chlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity against Chlamydia and other infectious and noninfectious diseases by vaccines.

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Section: Discussionmentioning

confidence: 99%

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

et al. 2015

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“…IL-10 binds to a heterodimeric IL-10 receptor complex consisting of the constitutively-expressed IL-10R2 subunit and the activation-induced IL-10R1 subunit. IL-10 signaling activates the Jak-STAT pathway [12]. The immunosuppressive effects of IL-10 in APCs are primarily mediated by phosphorylation of STAT3 [13].…”

Section: Overview Of Il-10 Production and Signalingmentioning

confidence: 99%

Suppression of antigen presentation by IL-10

Mittal

Roche

2015

Current Opinion in Immunology

237

151

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Regulated antigen presentation to immune cells determines the effectiveness of an immune response. IL-10 is an immunosuppressive cytokine that regulates immune responses by inhibiting the ability of APCs to present antigens to T cells in a variety of ways. The mechanisms of IL-10-mediated immunosuppression include interference in TLR- or IFNγ-medited dendritic cell (DC) and macrophage activation as well as direct induction of genes that suppress APC function. In this review we will discuss current studies exploring the molecular mechanisms by which IL-10 suppresses APC function.

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“…of Transcription (JAK-STAT) signaling axis of host responses. [ 6 ] IL-10 was first identified by its ability to stop the immune response by inhibiting the production of a number of cytokines. [ 7 ] IL-10 has been recognized to have potent and broad-spectrum anti-inflammatory activity, which has been unequivocally established in various models of infection, inflammation, and even in cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Lactobacillus rhamnosus , for example, as a normal microbe inhabitant of the placental mucosa, triggers signaling pathways involving IL-10 and JAK-STAT to control tumor necrosis factor (TNF)-α production, which prevents preterm birth. [ 6 9 ]…”

Section: Introductionmentioning

confidence: 99%

“…Interleukin-10 is known to control or prevent production of TNF-α, IL-6 and other mediators. [ 6 ] A meta-analysis has provided strong evidence that IL-10 is associated with risk of T2DM. [ 10 ] With regard to CPD, IL-10 levels were higher in healthy controls as compared with chronic periodontitis patients[ 11 ] and lower levels of IL-10 in aggressive periodontitis has been reported.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of serum interleukin-10 levels as a predictor of glycemic alteration in chronic periodontitis and type 2 diabetes mellitus

Acharya¹,

Thakur²,

Muddapur³

2015

J Indian Soc Periodontol

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Aim:Chronic periodontal disease (CPD) and type 2 diabetes mellitus (T2DM) share common pathogenic pathways. This study aimed to estimate levels of serum interleukin (IL-10), an anti-inflammatory cytokine also associated with T2DM and evaluate its association with hyperglycemia.Materials and Methods:This investigation involved sixty participants divided into four groups comprising 15 participants each: Group 1 (healthy controls), Group 2 (CPD patients), Group 3 (T2DM patients with CPD) and Group 4 (T2DM patients). Plaque index, gingival index, probing pocket depths (PPD), clinical attachment loss, bleeding on probing, random blood sugar, glycosylated hemoglobin (HbA1c), and serum IL-10 was measured.Results:Interleukin-10 was detected in all four groups. Statistically significant (P < 0.05) differences were observed in most of the variables in all groups. IL-10 correlated significantly with PPD in Group 1 and with HbA1c in Group 4. IL-10 regressed with PPD in Group 1 and with HbA1c in Group 4. IL-10 levels were lower in Group 3 when compared with Group 4 and was lowest in Group 2.Conclusion:Low IL-10 levels associated with high HbA1c. Pathogenic mechanisms of CPD seem to regulate IL-10. Serum IL-10 levels may be one of the predictors of glycemia.

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Infection-induced IL-10 and JAK-STAT

Cited by 58 publications

References 107 publications

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

Suppression of antigen presentation by IL-10

Evaluation of serum interleukin-10 levels as a predictor of glycemic alteration in chronic periodontitis and type 2 diabetes mellitus

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