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

Tomas Blanco; Rohan Bir Singh; Hayate Nakagawa; Yukako Taketani; Thomas H Dohlman; Yihe Chen; Sunil K Chauhan; Jia Yin; Reza Dana

doi:10.1016/j.mucimm.2022.12.002

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

Mucosal Immunol. 2023 Oct;16(5):711-726. doi: 10.1016/j.mucimm.2022.12.002. Epub 2023 Jan 13.

Authors

Tomas Blanco¹, Rohan Bir Singh¹, Hayate Nakagawa¹, Yukako Taketani¹, Thomas H Dohlman¹, Yihe Chen¹, Sunil K Chauhan¹, Jia Yin¹, Reza Dana²

Affiliations

¹ Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, USA.
² Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, USA. Electronic address: Reza_Dana@meei.harvard.edu.

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.

Keywords: CD103(+) DC; Cornea; Corneal transplantation; Dendritic Cells; Penetrating Keratoplasty; Th1 cells; Treg cells.

Abstract

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