Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université Paul Sabatier Toulouse III, Toulouse, France.
Front Immunol. 2020 Mar 31;11:453. doi: 10.3389/fimmu.2020.00453. eCollection 2020.
Dendritic cells (DCs) form a collection of antigen-presenting cells (APCs) that are distributed throughout the body. Conventional DCs (cDCs), which include the cDC1 and cDC2 subsets, and plasmacytoid DCs (pDCs) constitute the two major ontogenically distinct DC populations. The pDCs complete their differentiation in the bone marrow (BM), whereas the cDC subsets derive from pre-committed BM precursors, the pre-cDC, that seed lymphoid and non-lymphoid tissues where they further differentiate into mature cDC1 and cDC2. Within different tissues, cDCs express distinct phenotype and function. Notably, cDCs in the thymus are exquisitely efficient at processing and presenting antigens in the class II pathway, whereas in the spleen they do so only upon maturation induced by danger signals. To appraise this functional heterogeneity, we examined the regulation of the expression of distinct antigen-processing enzymes during DC ontogeny. We analyzed the expression of cathepsin S (CTSS), cathepsin L (CTSL), and thymus-specific serine protease (TSSP), three major antigen-processing enzymes regulating class II presentation in cDC, by DC BM precursors and immature and mature cDCs from the spleen and thymus. We found that pre-cDCs in the BM express relatively high levels of these different proteases. Then, their expression is modulated in a tissue-specific and subset-specific manner with immature and mature thymic cDCs expressing overall higher levels than immature splenic cDCs. On the other hand, the TSSP expression level is selectively down-regulated in spleen pDCs, whereas CTSS and CTSL are both increased in thymic and splenic pDCs. Hence, tissue-specific factors program the expression levels of these different proteases during DC differentiation, thus conferring tissue-specific function to the different DC subsets.
树突状细胞 (DC) 形成了一组分布于全身的抗原呈递细胞 (APC)。传统的 DC (cDC)，包括 cDC1 和 cDC2 亚群，以及浆细胞样 DC (pDC)，构成了两种主要的不同发育来源的 DC 群体。pDC 在骨髓 (BM) 中完成分化，而 cDC 亚群则来源于预先确定的 BM 前体，即前 cDC，它们在淋巴组织和非淋巴组织中进一步分化为成熟的 cDC1 和 cDC2。在不同的组织中，cDC 表现出不同的表型和功能。值得注意的是，胸腺中的 cDC 在 II 类途径中处理和呈递抗原的效率极高，而在脾脏中，只有在危险信号诱导成熟后才会这样做。为了评估这种功能异质性，我们研究了在 DC 发育过程中不同抗原处理酶的表达调控。我们分析了组织蛋白酶 S (CTSS)、组织蛋白酶 L (CTSL) 和胸腺特异性丝氨酸蛋白酶 (TSSP) 的表达，这三种主要的抗原处理酶调节 cDC 中的 II 类呈递，通过 BM 前体和来自脾脏和胸腺的未成熟和成熟 cDC 进行分析。我们发现，BM 中的前 cDC 表达相对高水平的这些不同的蛋白酶。然后，它们的表达以组织特异性和亚群特异性的方式进行调节，未成熟和成熟的胸腺 cDC 表达的总体水平高于未成熟的脾脏 cDC。另一方面，TSSP 的表达水平在脾脏 pDC 中选择性地下调，而 CTSS 和 CTSL 在胸腺和脾脏 pDC 中均增加。因此，组织特异性因子在 DC 分化过程中编程这些不同蛋白酶的表达水平，从而为不同的 DC 亚群赋予组织特异性功能。
