1. Academic Validation
  2. IL-27 Regulated CD4+IL-10+ T Cells in Experimental Sjögren Syndrome

IL-27 Regulated CD4+IL-10+ T Cells in Experimental Sjögren Syndrome

  • Front Immunol. 2020 Aug 11;11:1699. doi: 10.3389/fimmu.2020.01699.
Jingjing Qi 1 2 Zhuoya Zhang 1 Xiaojun Tang 1 Wenchao Li 1 Weiwei Chen 1 Genhong Yao 1
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
  • 2 Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning, China.
Abstract

Interleukin 27 (IL-27) plays diverse immune regulatory roles in autoimmune disorders and promotes the generation of IL-10-producing CD4+ T cells characterized by producing the immunosuppressive cytokine IL-10. However, whether IL-27 participates in pathological progress of Sjögren syndrome (SS) through regulating CD4+IL-10+ T cells remains unknown. Here we aimed to explore the potential role of IL-27 and CD4+IL-10+ T cells in the pathogenesis of SS. The IL-27 gene knockout non-obese diabetic (IL-27-/-NOD) mice were generated and injected with exogenous IL-27. Exogenous injection of IL-27 and neutralization of IL-27 with anti-IL-27 antibody in NOD mice were performed. The histopathologic changes in submandibular glands, lacrimal glands and lung, salivary flow rate, and percentages of CD4+IL-10+ T cells were determined. And, ovalbumin-immunized C57L/B6 mice were injected with IL-27 to detect the percentage of CD4+IL-10+ T cells. In vitro, splenic naive T cells from C57L/B6 mice were cultured with IL-27 for 4 days to induce the differentiation of CD4+IL-10+ T cells. In addition, IL-27, IL-10, and CD4+IL-10+ T cells were determined in health control and SS patients. The results showed that IL-27-/-NOD mice had more severe disease and lower level of CD4+IL-10+ T cells than control mice. And IL-27 promoted the generation and differentiation of CD4+IL-10+ T cells in vivo and in vitro significantly. In agreement with the findings in the SS-like mice, patients with SS showed lower levels of IL-27, IL-10, and CD4+IL-10+ T cells. Our findings indicated that IL-27 deficiency aggravated SS by regulating CD4+IL-10+ T cells. Targeting IL-27 and CD4+IL-10+ T cells may be a novel therapy for patients with SS.

Keywords

CD4+IL-10+ T cells; Sjögren syndrome; immunosuppression; interleukin-10; interleukin-27.

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