CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell-derived DCs (MoDCs) inhibited the proliferation of CD4⁺ T cells and the differentiation into IFN-γ-producing T helper 1 (Th1) cells, which were critical in acute graft-versus-host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo-BMT) murine models, we consistently found that CD11c-deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN-γ-expressing CD4⁺ Th1 cells and CD8⁺ T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen presentation of APCs. CD11c-deficient bone marrow-derived DCs (BMDCs) impaired the antigen presentation function in coculture assay. Mechanistically, CD11c interacted with MHCII and Hsp90 and participated in the phosphorylation of Akt and Erk1/2 in DCs after multiple inflammatory stimulations. Therefore, CD11c played crucial roles in triggering aGVHD and might serve as a potential target for the prevention and treatment of aGVHD.

中文翻译：

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CD11c 参与触发骨髓移植期间的急性移植物抗宿主病

CD11c 是一种典型的树突状细胞 (DC) 标记物，在免疫系统中的功能定义不明确。在这里，我们发现阻断人外周血单核细胞衍生的 DC (MoDC) 上的 CD11c 会抑制 CD4 ⁺ T 细胞的增殖和向产生 IFN-γ 的 T 辅助 1 (Th1) 细胞的分化，这在急性移植中至关重要抗宿主病 (aGVHD) 发病机制。使用同种异体骨髓移植 (allo-BMT) 小鼠模型，我们一致发现 CD11c 缺陷的受体小鼠因表达 IFN-γ 的 CD4 ⁺ Th1 细胞和 CD8 ⁺减少而减轻了 aGVHD 症状。T细胞。转录分析表明，CD11c 参与了多种免疫调节功能，包括维持 APC 的抗原呈递。CD11c 缺陷的骨髓源性 DCs (BMDCs) 在共培养试验中损害了抗原呈递功能。从机制上讲，CD11c 与 MHCII 和 Hsp90 相互作用，并在多次炎症刺激后参与 DCs 中 Akt 和 Erk1/2 的磷酸化。因此，CD11c 在触发 aGVHD 中发挥了至关重要的作用，可能成为预防和治疗 aGVHD 的潜在靶点。