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Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-beta

机译:基质细胞通过调节TGF-β的激活来控制DC和记忆T细胞的上皮细胞驻留

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摘要

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-beta 1 (TGF-beta) for epidermal residence. Here we found that integrins alpha(v)beta(6) and alpha(v)beta(8) were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-beta. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required alpha v beta(6). Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-beta, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-beta by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.
机译:驻留在屏障上皮中的免疫系统细胞为抵抗病原体提供了第一道防线。朗格汉斯细胞(LCs)和CD8(+)组织驻留性记忆T细胞(TRM细胞)需要活性转化生长因子-β1(TGF-β)用于表皮驻留。在这里,我们发现整联蛋白alpha(v)beta(6)和alpha(v)beta(8)通过角质形成细胞(KC)以非重叠模式表达,并通过激活潜在的TGF-beta保持了LC和TRM细胞的表皮滞留。同样,树突状细胞和TRM细胞在小肠上皮中的驻留也需要alpha v beta(6)。用紫外线照射治疗皮肤会降低KCs上整联蛋白的表达,并降低活性TGF-β的可用性,从而导致LC迁移。我们的数据表明,基质细胞对TGF-β的激活调控能够通过一种新型的细胞间通讯机制直接控制免疫系统细胞的上皮驻留。

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