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Yu H , Tian Y , Wang Y , Mineishi S , Zhang Y
Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance
Front Immunol. 2019 ;10 :93
PMID: 30774630    PMCID: PMC6367268   
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Graft-vs.-host disease (GVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Significant progresses have been made in defining the dichotomous role of dendritic cells (DCs) in the development of GVHD. Host-derived DCs are important to elicit allogeneic T cell responses, whereas certain donor-types of DCs derived from newly engrafted hematopoietic stem/progenitor cells (HSPCs) can amply this graft-vs.-host reaction. In contrast, some DCs also play non-redundant roles in mediating immune tolerance. They induce apoptotic deletion of host-reactive donor T cells while promoting expansion and function of regulatory T cells (Treg). Unfortunately, this tolerogenic effect of DCs is impaired during GVHD. Severe GVHD in patients subject to allo-HSCT is associated with significantly decreased number of circulating peripheral blood DCs during engraftment. Existing studies reveal that GVHD causes delayed reconstitution of donor DCs from engrafted HSPCs, impairs the antigen presentation function of newly generated DCs and reduces the capacity of DCs to regulate Treg. The present review will discuss the importance of DCs in alloimmunity and the mechanism underlying DC reconstitution after allo-HSCT.
1664-3224 Yu, Hongshuang Tian, Yuanyuan Wang, Ying Mineishi, Shin Zhang, Yi R01 CA172106/CA/NCI NIH HHS/United States R01 HL127351/HL/NHLBI NIH HHS/United States Journal Article Review Switzerland Front Immunol. 2019 Feb 1;10:93. doi: 10.3389/fimmu.2019.00093. eCollection 2019.