TSLP-targeting therapy: Beyond allergy?

TSLP-targeting therapy: Beyond allergy?
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DOI:
10.1002/ctm2.1241
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发表时间:
2023-05
影响因子:
10.6
通讯作者:
--
中科院分区:
医学2区
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--
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胸腺基质淋巴细胞生成素(TSLP)是一种I型四α-螺旋束细胞因子1,其由上皮细胞;肺、皮肤和胃肠道中的基质细胞;造血细胞,包括树突状细胞(DC)、嗜碱性粒细胞和肥大细胞;和毛囊产生。2机械损伤、TLR 2/NOD 2、蠕虫感染、炎性细胞因子和蛋白酶触发这些细胞产生TSLP。促炎细胞因子和Th 2相关细胞因子也诱导炎症条件期间TSLP的产生。2 TSLP在体内平衡和病理条件下具有多种功能,该细胞因子可作用于B细胞、DC、CD 4+和CD 8 + T细胞、中性粒细胞、肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞、2型先天性淋巴样细胞、自然杀伤T细胞、平滑肌细胞甚至肿瘤细胞。2 TSLP与白细胞介素(IL)-7具有同源性,并通过靶细胞表面的TSLPR(由CRLF 2基因编码)和IL-7 R α的异源二聚体进行信号传导,而IL-7则通过IL-7 R α和共同的细胞因子受体γ链(γc)进行信号传导,γ c与TSLP具有同源性。
Thymic stromal lymphopoietin (TSLP) is a type I fouralpha-helical-bundle cytokine 1 that is produced by epithelial cells; stromal cells in the lungs, skin and gastrointestinal tract; haematopoietic cells, including dendritic cells (DCs), basophils and mast cells; and hair follicles. 2 Mechanical injury, TLR2/NOD2, helminth infection, inflammatory cytokines and proteases trigger the production of TSLP by these cells. Pro-inflammatory cytokines and Th2-related cytokines also induce TSLP production during inflammatory conditions. 2 TSLP has multiple functions in both homeostasis and pathological conditions, and this cytokine can act on B cells, DCs, CD4+ and CD8+ T cells, neutrophils, mast cells, basophils, eosinophils, type 2 innate lymphoid cells, natural killer T cells, smooth muscle cells and even tumour cells. 2 TSLP shares homology with interleukin (IL)-7 and signals via a heterodimer of TSLPR (encoded by the CRLF2 gene) and IL-7Rα on the surface of target cells, whereas IL-7 instead signals via IL-7Rα and the common cytokine receptor γ chain (γc), which shares
TSLP和IL-7使用两种不同的机制来调节人CD4+ T细胞稳态。
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