| First Author | Michaels Lopez V | Year | 2022 |
| Journal | J Leukoc Biol | Volume | 112 |
| Issue | 4 | Pages | 629-639 |
| PubMed ID | 35224773 | Mgi Jnum | J:330060 |
| Mgi Id | MGI:7356536 | Doi | 10.1002/JLB.1A0921-502RR |
| Citation | Michaels Lopez V, et al. (2022) Intrathymic SIRPa cDC subsets organization in normal and stress conditions reveal another level of cDCs heterogeneity. J Leukoc Biol 112(4):629-639 |
| abstractText | Three major subsets constitute the dendritic cells (DCs) pool in the thymus. They play key roles in self-antigen-specific thymocyte deletion and in the development of immunoregulatory T cells. Resident SIRPa(-) conventional DCs (cDCs, CD11c(+) PDCA1(lo) ) are derived from intrathymic progenitors, whereas migratory SIRPa(+) cDCs and plasmacytoid DCs (pDCs, CD11c(+) PDCA1(+) ) originate from extrathymic sites. Here, we describe the organization and the shaping of cDC populations at the steady state and under stress conditions in wild-type and mutant mice (CD3eKO, IL7RaKO, and Flt3LKO). In neonates, the thymus is mainly composed of SIRPa(-) -resident cDCs, whereas both cDC subsets are present in equal proportions in the adult. Upon thymus colonization, migratory SIRPa(+) cDCs gain expression of phenotypic markers in a microenvironment dependent way. Here, we show that both processes are deeply impacted by mutations affecting T cell development. Under stress conditions such as sublethal irradiation, intrathymic resident SIRPa(-) cDCs are the first to regenerate the thymic cDC pool. Upon bone marrow transplantation, migratory SIRPa(+) cDCs become the main source of thymic cDCs. These successive waves of regeneration eventually lead to a balance between resident and migratory DCs within the newly colonized thymus. These findings highlight an unrevealed division of labor between resident and migratory subsets for the organization/establishment of the thymic cDC compartment. |
