Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4+CD25+ regulatory T cells

Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated imm...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2020-01, Vol.24 (2), p.2027-2039
Main Authors: Ge, Yun, Huang, Man, Wu, Yao, Dong, Ning, Yao, Yong‐Ming
Format: Article
Language:English
Subjects:
Animals
Arthritis
CD25 antigen
CD4 antigen
CD4 Antigens - metabolism
Cell proliferation
Cloning
CTLA-4 Antigen - metabolism
Cytokines
Depletion
Down-Regulation - genetics
Effector cells
Experiments
Flow cytometry
Forkhead Transcription Factors - metabolism
Helper cells
Homeostasis
Immune response
Immunoglobulins
Immunoregulation
Immunosuppression
Immunosuppressive agents
Interferon-gamma - metabolism
Interleukin-1 - metabolism
Interleukin-10 - biosynthesis
Interleukin-2 - metabolism
Interleukin-2 Receptor alpha Subunit - metabolism
Interleukin-4 - metabolism
interleukin‐38
Laboratory animals
Lipopolysaccharides
Lymphocytes
Lymphocytes T
Male
Mice, Inbred BALB C
Monoclonal antibodies
Mortality
Original
regulatory T cells
Sepsis
Sepsis - immunology
Stimulation
Survival Analysis
T-Lymphocytes, Regulatory - immunology
Transforming Growth Factor beta1 - metabolism
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Summary:Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated immune response of CD4+CD25+ Tregs in sepsis. Here, we provide evidence that expressions of IL‐38 and its receptor were detected in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up‐regulated the expression of IL‐38. Treatment with rmIL‐38 dramatically enhanced the immunosuppressive activity of CD4+CD25+ Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti–IL‐38 antibody was administered. Administration of rmIL‐38 improved the survival rate of CLP mice. In addition, CD4+CD25+ Tregs depletion before the onset of sepsis obviously abolished IL‐38–mediated protective response. These findings suggest that IL‐38 enhances the immunosuppressive activity of CD4+CD25+ Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.14902