| First Author | Wang Q | Year | 2021 |
| Journal | Immunology | Volume | 164 |
| Issue | 1 | Pages | 148-160 |
| PubMed ID | 33934334 | Mgi Jnum | J:322195 |
| Mgi Id | MGI:6752481 | Doi | 10.1111/imm.13350 |
| Citation | Wang Q, et al. (2021) CD11c participates in triggering acute graft-versus-host disease during bone marrow transplantation. Immunology 164(1):148-160 |
| abstractText | 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-gamma-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-gamma-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. |
