CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment.

ABSTRACT: Upon recognition of auto-antigens, thymocytes are negatively selected or diverted to a regulatory T cell (Treg) fate. CCR7 is required for negative selection of auto-reactive thymocytes in the thymic medulla. Here, we describe an unanticipated contribution of CCR7 to intrathymic Treg generation. Ccr7^-/- mice have increased Treg cellularity because of a hematopoietic but non-T cell autonomous CCR7 function. CCR7 expression by thymic dendritic cells (DCs) promotes survival of mature Sirpα^- DCs. Thus, CCR7 deficiency results in apoptosis of Sirpα^- DCs, which is counterbalanced by expansion of immature Sirpα⁺ DCs that efficiently induce Treg generation. CCR7 deficiency results in enhanced intrathymic generation of Tregs at the neonatal stage and in l

SUBMITTER: Hu Z 

PROVIDER: S-EPMC5639943 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature