Maiti George, Frikeche Jihane, Loomis Cynthia, Chakravarti Shukti
bioRxiv. 2024 Oct 23:2024.10.20.619307. doi: 10.1101/2024.10.20.619307.
The extracellular matrix (ECM) is known to regulate innate immune cells but its role in T cell functions is poorly understood. Here, we show a protective role for ECM proteoglycans, lumican and biglycan in hapten-induced contact dermatitis that is achieved through limiting proinflammatory CD4 T cells. Lumican and biglycan-null mice develop significant inflammation with greater numbers of CD4 T cells in hapten-challenged ear pinnae, while their draining lymph nodes show increased T-bet-STAT1 signaling, Th1 commitment, and IFN-γ secreting CD4 T cell proliferation. Wild type mouse lymph node fibroblastic reticular cells secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. , lumican and biglycan co-localize with LFA-1 on T cell surfaces, and all three proteoglycans suppress LFA-1 mediated T cell activation. Overall, this study elucidates a novel paracrine regulation of Th1 cells by ECM proteoglycans to limit inflammation and tissue damage.
细胞外基质（ECM）已知可调节先天性免疫细胞，但其在T细胞功能中的作用却知之甚少。在此，我们展示了ECM蛋白聚糖、核心蛋白聚糖和双糖链蛋白聚糖在半抗原诱导的接触性皮炎中的保护作用，这种作用是通过限制促炎性CD4 + T细胞来实现的。缺乏核心蛋白聚糖和双糖链蛋白聚糖的小鼠在半抗原攻击的耳廓中出现明显炎症，CD4 + T细胞数量增多，而其引流淋巴结显示T-bet-STAT1信号增强、Th1分化以及分泌IFN-γ的CD4 + T细胞增殖增加。野生型小鼠淋巴结成纤维网状细胞分泌核心蛋白聚糖、双糖链蛋白聚糖和一种相关蛋白聚糖饰胶蛋白聚糖，而幼稚或活化的T细胞均不表达这些蛋白聚糖。此外，核心蛋白聚糖和双糖链蛋白聚糖与T细胞表面的淋巴细胞功能相关抗原-1（LFA-1）共定位，并且这三种蛋白聚糖均抑制LFA-1介导的T细胞活化。总体而言，本研究阐明了ECM蛋白聚糖对Th1细胞的一种新的旁分泌调节作用，以限制炎症和组织损伤。
