Interleukin‐27 as a Negative Regulator of Human Neutrophil Function

Li, Jianping; Wu, Hao; Xing, Wen; Yang, Shangda; Lu, Shi Hong; Du, Wei; Yu, Jiaojiao; Chen, F.; Zhang, L.; Han, Zhongchao

doi:10.1111/j.1365-3083.2010.02422.x

Cited by 32 publications

(35 citation statements)

References 37 publications

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“…In addition we found that the chemokine production of endothelial cells upon stimulation with IL-1β or IL-6 was suppressed by IL-27. Moreover, IL-27 has been reported to directly affect adhesion and activation of neutrophils [55].…”

Section: Discussionmentioning

confidence: 99%

Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza

et al. 2014

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Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show that the cytokine IL-27 plays a crucial role in protection from exaggerated inflammation during influenza virus infection. Using Il-27ra −/− mice, IL-27 was found to limit immunopathology, neutrophil accumulation, and dampened TH1 or TH17 responses via IL-10–dependent and -independent pathways. Accordingly, the absence of IL-27 signals resulted in a more severe disease course and in diminished survival without impacting viral loads. Consistent with the delayed expression of endogenous Il-27p28 during influenza, systemic treatment with recombinant IL-27 starting at the peak of virus load resulted in a major amelioration of lung pathology, strongly reduced leukocyte infiltration and improved survival without affecting viral clearance. In contrast, early application of IL-27 impaired virus clearance and worsened disease. These findings demonstrate the importance of IL-27 for the physiological control of immunopathology and the potential value of well-timed IL-27 application to treat life-threatening inflammation during lung infection.

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Section: Discussionmentioning

confidence: 99%

Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza

et al. 2014

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“…Knowledge of IL-27 functionality has largely come from T cell biology, and its role in the adaptive immune response is well described 12–14 . However, the IL-27 receptor complex is also expressed on other immune cell types, including granulocytes 16 and macrophages 17 , indicating that the functional capabilities of IL27 may be even wider and in particular IL27 may play a role in mediating innate immunity. Indeed, IL-27 can impact the function of innate cell subsets, including macrophages 18 , neutrophils 16, 19 , and dendritic cells 20–22 .…”

Section: Introductionmentioning

confidence: 99%

Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through Interleukin-10–Dependent, T-Cell–Independent Attenuation of Colonic Mucosal Innate Immune Responses

McLean

Andrews

Hanson

et al. 2017

Inflammatory Bowel Diseases

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Background IBD patients with acute severe colitis face systemic anti-TNF biologic rescue therapy or colectomy, if treatment with intravenous steroids fail. Interleukin (IL)-27 is a cytokine with an immunosuppressive role in adaptive immune responses. However, the IL-27 receptor complex is also expressed on innate immune cells, and there is evidence that IL-27 can impact the function of innate cell subsets, although this particular functionality in vivo is not understood. Our aim was to define the efficacy of IL-27 in acute severe colitis and characterize novel IL-27 driven mechanisms of immunosuppression in the colonic mucosa. Methods We assessed oral delivery of Lactococcus lactis expressing an IL-27 hyperkine on the innate immune response in vivo in a genetically intact, non-infective acute murine colitis model induced by intra-rectal instillation of 2,4,6-Trinitrobenzenesulfonic acid in SJL/J mice. Results IL-27 attenuates acute severe colitis through reduction of colonic mucosal neutrophil infiltrate associated with a decreased CXC chemokine gradient. This suppression was T cell-independent and IL-10-dependent, initially featuring enhanced mucosal IL-10. IL-27 was associated with a reduction in colonic pro-inflammatory cytokines and induced a multifocal strong positive nuclear expression of phosphorylated STAT-1 in mucosal epithelial cells. Conclusion We have defined novel mechanisms of IL-27 immunosuppression towards colonic innate immune responses in vivo. Mucosal delivery of IL-27 has translational potential as a novel therapeutic for IBD and is a future mucosal directed rescue therapy in acute severe inflammatory bowel disease.

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“…On the other hand, there are several reports that demonstrated that IL-27 inhibited Th2 and Th17 responses [16, 17]. It is known that IL-27 could suppress neutrophil function to inhibit neutrophil adhesion [18]. It was reported IL-27 is expressed in gingival crevicular fluid of human subjects [19].…”

Section: Introductionmentioning

confidence: 99%

IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells

Hosokawa

Ozaki

et al. 2017

Cell Physiol Biochem

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Background/Aims: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). Methods: We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. Results: IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. Conclusion: IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.

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Interleukin‐27 as a Negative Regulator of Human Neutrophil Function

Cited by 32 publications

References 37 publications

Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza

Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza

Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through Interleukin-10–Dependent, T-Cell–Independent Attenuation of Colonic Mucosal Innate Immune Responses

IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells

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