Kanayama Masashi, Izumi Yuta, Onai Nobuyuki, Akashi Takako, Hiraoka Yuichi, Ohteki Toshiaki
Department of Biodefense Research, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo [formerly Medical Research Institute, Tokyo Medical and Dental University (TMDU)], Tokyo, Japan.
Department of Immunology, Kanazawa Medical University, Ishikawa, Japan.
Sci Adv. 2025 Jun 6;11(23):eadt4909. doi: 10.1126/sciadv.adt4909.
Conventional dendritic cells (cDCs) regulate adaptive immunity. Although most cDCs are of myeloid origin (M-cDCs), some cDCs originate from pro-plasmacytoid DCs (pro-pDCs) via pDC-like cells [lymphoid cDCs (L-cDCs)]. Using lymphoid progenitor-tracking systems, we report tissue segregation, a unique differentiation pathway, and the functions of L-cDCs. Notably, L-cDC2s are predominantly distributed in barrier tissues such as the lungs and skin. Single-cell RNA-sequencing analysis revealed the enrichment of lymphocyte signature genes in L-cDCs. We identified lymphocyte-primed cDC precursors, which are distinct from pDC-like cells, as sources of L-cDCs. Compared with M-cDC2s, L-cDC2s weakly primed T cells under low-dose antigen stimulation and preferentially promoted T helper 2 (T2) differentiation under sufficient antigenic stimulation. These results suggest the diverse developmental pathways of L-cDCs and imply the contribution of L-cDCs to tolerance and hyperresponses to T2-related antigens in barrier tissues.
传统树突状细胞（cDCs）调节适应性免疫。尽管大多数cDCs起源于髓系（M-cDCs），但一些cDCs通过类浆细胞样树突状细胞（pDC样细胞）从浆细胞样前体树突状细胞（pro-pDCs）起源[淋巴样cDCs（L-cDCs）]。利用淋巴样祖细胞追踪系统，我们报告了L-cDCs的组织分隔、独特的分化途径及其功能。值得注意的是，L-cDC2s主要分布在肺和皮肤等屏障组织中。单细胞RNA测序分析揭示了L-cDCs中淋巴细胞特征基因的富集。我们确定了淋巴细胞启动的cDC前体，它不同于pDC样细胞，是L-cDCs的来源。与M-cDC2s相比，L-cDC2s在低剂量抗原刺激下对T细胞的启动作用较弱，而在足够的抗原刺激下优先促进辅助性T细胞2（T2）分化。这些结果提示了L-cDCs的多种发育途径，并暗示了L-cDCs对屏障组织中T2相关抗原的耐受性和高反应性的贡献。
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