CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells

Marc Clement, Giulia Fornasa, Kevin Guedj, Sanae Ben Mkaddem, Anh Thu Gaston, Jamila Khallou-Laschet, Marion Morvan, Antonino Nicoletti, Giuseppina Caligiuri

Research output: Contribution to journalArticlepeer-review

Abstract

CD31 is a transhomophilic tyrosine-based inhibitory motif receptor and is expressed by both dendritic cells (DCs) and T lymphocytes. Previous studies have established that the engagement of CD31 drives immune-inhibitory signaling in T lymphocytes, but the effect exerted by CD31 signaling in DCs remains elusive. Here, we show that CD31 is a key coinhibitory receptor on stimulated DCs, favoring the development of tolerogenic functions and finally resulting in T-cell tolerance. The disruption of CD31 signaling favored the immunogenic maturation and migration of resident DCs to the draining lymph nodes. In contrast, sustaining the CD31/SHP-1 signaling during DC maturation resulted in reduced NF-κB nuclear translocation, expression of costimulatory molecules, and production of immunogenic cytokines (e.g., IL-12, IL-6), whereas the expression of TGF-β and IL-10 were increased. More importantly, CD31-conditioned DCs purified from the draining lymph nodes of ovalbumin-immunized mice favored the generation of antigen-specific regulatory T cells (CD25+ forkhead box P3+) at the expense of effector (IFN-γ+) cells upon coculture with naive ovalbumin-specific CD4+ T lymphocytes ex vivo. Finally, the adoptive transfer of CD31-conditioned myelin oligodendrocyte glycoprotein-loaded DCs carried immune tolerance against the subsequent development of MOG-induced experimental autoimmune encephalomyelitis in vivo. The key coinhibitory role exerted by CD31 on DCs high-lighted by the present study may have important implications both in settings where the immunogenic function of DCs is desirable, such as infection and cancer, and in settings where tolerance-driving DCs are preferred, such as autoimmune diseases and transplantation.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number12
DOIs
Publication statusPublished - Mar 25 2014

Keywords

  • CD31 tolerance
  • EAE
  • NFkB
  • Treg

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells'. Together they form a unique fingerprint.

Cite this