Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy.
Istituto Ortopedico Galeazzi, 20100 Milano, Italy.
Int J Mol Sci. 2021 Jul 28;22(15):8076. doi: 10.3390/ijms22158076.
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.
银屑病（PS）是一种具有自身免疫特征的皮肤病，由免疫细胞介导，通常表现为炎症性红斑斑块，并与许多合并症相关。PS 表现出过度的角质形成细胞增殖和大量免疫细胞，包括巨噬细胞、中性粒细胞、Th1 和 Th17 淋巴细胞和肥大细胞（MCs）。MCs 具有造血起源，来源于骨髓细胞，这些细胞迁移、成熟并驻留在血管化组织中。它们可以通过抗原引发的促炎细胞因子过度表达而被激活，并释放包括白细胞介素（IL）-1 和 IL-33 在内的许多介质。由激活的角质形成细胞和 MCs 释放的 IL-1 刺激皮肤巨噬细胞释放 IL-36-a 强有力的促炎 IL-1 家族成员。IL-36 介导先天和适应性免疫，包括银屑病等慢性炎症性疾病。抑制 IL-36 可能导致银屑病治疗的显著改善。IL-36 被 IL-36Ra 抑制，IL-36Ra 与 IL-36 受体配体结合，但也可以通过将 IL-38 与 IL-36 受体（IL-36R）结合来抑制。IL-38 仅特异性结合 IL-36R，并抑制体外用 IL-36 刺激的人单核细胞，与 IL-36Ra 具有相同的作用。在这里，我们报告说 MCs 产生的 IL-1 介导了银屑病中的炎症-这一过程激活巨噬细胞分泌受 IL-38 抑制的促炎 IL-36。IL-37 属于 IL-1 家族，通过抑制 IL-1 广泛抑制先天炎症。在炎症性关节炎的鼠模型中，IL-37 通过抑制 IL-1 导致关节炎症的抑制。因此，认为 IL-37 可以在炎症性银屑病中发挥抑制作用是恰当的。在本文中，我们证实 IL-38 和 IL-37 细胞因子作为银屑病炎症的抑制剂出现，并有望成为一种创新的治疗工具。
