Premium
SIRP α/ CD 47 axis controls the maintenance of transplant tolerance sustained by myeloid‐derived suppressor cells
Author(s) -
Pengam Sabrina,
Durand Justine,
Usal Claire,
Gauttier Vanessa,
Dilek Nahzli,
Martinet Bernard,
Daguin Véronique,
Mary Caroline,
Thepenier Virginie,
Teppaz Géraldine,
Renaudin Karine,
Blancho Gilles,
Vanhove Bernard,
Poirier Nicolas
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15497
Subject(s) - cd47 , myeloid derived suppressor cell , immunology , chemokine , myeloid , immune system , immune tolerance , medicine , cancer research , cancer , suppressor
Myeloid‐derived suppressor cells ( MDSC ) are a heterogeneous population of immature hematopoietic precursors known to suppress immune responses. Interaction of SIRP alpha ( SIRP α), expressed by myeloid cells, with the ubiquitous receptor CD 47 is an important immune checkpoint of the innate response regulating macrophages and dendritic cells functions. We previously described that MDSC expressing SIRP α accumulated after transplantation and maintained kidney allograft tolerance. However, the role of the SIRP α/ CD 47 axis on MDSC function remained unknown. Here, we found that blocking SIRP α or CD 47 with monoclonal antibodies ( mA bs) induced differentiation of MDSC into myeloid cells overexpressing MHC class II , CD 86 costimulatory molecule and increased secretion of macrophage‐recruiting chemokines (eg, MCP ‐1). Using a model of long‐term kidney allograft tolerance sustained by MDSC , we observed that administration of blocking anti‐ SIRP α or CD 47 mA bs induced graft dysfunction and rejection. Loss of tolerance came along with significant decrease of MDSC and increase in MCP ‐1 concentration in the periphery. Graft histological and transcriptomic analyses revealed an inflammatory (M1) macrophagic signature at rejection associated with overexpression of MCP ‐1 mRNA and protein in the graft. These findings indicate that the SIRP α‐ CD 47 axis regulates the immature phenotype and chemokine secretion of MDSC and contributes to the induction and the active maintenance of peripheral acquired immune tolerance.