Biology of <scp>IL</scp>‐38 and its role in disease

Veerdonk, Frank L. van de; Graaf, Dennis M. de; Joosten, Leo A. B.; Dinarello, Charles A.

doi:10.1111/imr.12612

Cited by 91 publications

(76 citation statements)

References 59 publications

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“…31,32 However, IL-38 does not appear to affect intrinsic antibacterial activity of phagocytes. 31,32 However, IL-38 does not appear to affect intrinsic antibacterial activity of phagocytes.…”

Section: Discussionmentioning

confidence: 98%

“…[31][32][33] There is growing interest in investigating the regulatory pathway of IL-38 in the pathogenesis of inflammatory and autoimmune disorders. (A, B) Flow cytometry plots showed CD4 + CD25 + Tregs in the spleen at 48 h after treatment with anti-CD25 antibody (PC61) (n = 6 per group).…”

Section: Discussionmentioning

confidence: 99%

“…31 Interestingly, IL-38 can be released from apoptotic cells to control inflammatory macrophage and Th17 response. IL-38 is extensively expressed in several tissues including spleen, thymus, foetal liver, placenta, lung and heart.…”

mentioning

confidence: 99%

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

Huang

et al. 2019

J Cellular Molecular Medi

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| INTRODUC TI ONCD4 + CD25 + regulatory T cells (Tregs) can regulate host responses to infections and tumours, and contribute to the prevention of allergies, autoimmune diseases and transplant rejection. 1-4 CD4 + CD25 + Tregs are essential for maintenance of immune homeostasis and self-tolerance. They express several crucial molecular markers, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, also termed CD152), glucocorticoid-induced tumour necrosis factor receptor (GITR) and forkhead/winged helix transcription factor p3 (Foxp3).Knockdown of these factors leads to lethal lymphoproliferative phenotypes. 5-8 Concomitantly, CD4 + CD25 + Tregs can produce various potent anti-inflammatory cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-β, which cause immunosuppression of effector T cells. 9-12 Moreover, CD4 + CD25 + Tregs can reduce IL-2 production and inhibit polyclonal T cell activity in vitro, 13 and Abstract 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. K E Y W O R D Simmune response, interleukin-38, regulatory T cells, sepsis

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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

Huang

et al. 2019

J Cellular Molecular Medi

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“…218 IL-36 is unique, in that in addition to having IL-36Ra, its actions can also be blocked by fellow family member IL-38. 219 IL-38 is able to block IL-36-driven IL-23/IL-17 axis and has been implicated in numerous arthritis models. 219 SNP in IL-38 has been associated with AS patients.…”

Section: Genetic Pointers Toward Il-23 In Enthesitismentioning

confidence: 99%

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Bridgewood

Sharif

Sherlock

et al. 2020

Immunological Reviews

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The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

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“…IL-38, like IL-37, suppresses innate inflammation and its role in immune responses and inflammation are presented in "Biology of IL-38 and its Role in Disease". 22 The volume closes with two reviews on the IL-1 Family of receptors. The IL-1 Receptor Family has a long history that began in 1988 with the identification of the IL-1R1, 23 followed by the report of homology of IL-1R1 with the Drosophila Toll protein 24 and completed in 1995 with discovery of the coreceptor, IL-1R3.…”

mentioning

confidence: 90%

Biology of IL‐38 and its role in disease

Cited by 91 publications

References 59 publications

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

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

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Introduction to the interleukin‐1 family of cytokines and receptors: Drivers of innate inflammation and acquired immunity

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Biology of IL‐38 and its role in disease

Cited by 91 publications

References 59 publications

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

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

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Introduction to the interleukin‐1 family of cytokines and receptors: Drivers of innate inflammation and acquired immunity

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

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