Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra
| Autor: | Rosa G. Bellomo, C E Gallenga, Pio Conti, Fabrizio Pregliasco, S K Kritas, Dorina Lauritano, Gianpaolo Ronconi, Caraffa A |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Review immunology 0302 clinical medicine cytokine Mast Cells Biology (General) Spectroscopy Skin LS7_9 Interleukin General Medicine psoriasis Acquired immune system Computer Science Applications Chemistry Cytokine 030220 oncology & carcinogenesis medicine.symptom QH301-705.5 Inflammation Catalysis Proinflammatory cytokine Inorganic Chemistry 03 medical and health sciences Immune system Psoriasis medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 business.industry IL-1 Interleukins Organic Chemistry Ambientale medicine.disease Interleukin-33 Interleukin 33 IL-38 Interleukin 1 Receptor Antagonist Protein 030104 developmental biology IL-1Ra IL-37 Immunology Mast cell inflammation business mast cell Interleukin-1 |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 8076, p 8076 (2021) International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36—a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs—a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool. |
| Databáze: | OpenAIRE |
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