Conventional type I migratory CD103⁺ dendritic cells are required for corneal allograft survival.

ABSTRACT: Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103⁺ dendritic cells (CD103⁺DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103⁺DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103⁺DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103⁺DC1 has been extensively studied in non-transplantation settings. We found that host CD103⁺DC1 infiltrates the corneal graft and migrates to the draining lymph nodes to suppress alloreactive CD4⁺ Th1 cells via the programmed death-ligand 1 axis. The systemic depletion of CD103⁺ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased rate of allograft rejection. Although allograft recipient Rag1 null mice reconstituted with naïve CD4⁺CD25^- T cells efficiently generated peripheral Treg cells (pTreg), the CD103⁺DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103⁺DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103⁺DC1 in regulating host alloimmune responses.

SUBMITTER: Blanco T 

PROVIDER: S-EPMC10413378 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature