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DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance

Authors
 Patricia Conde  ;  Mercedes Rodriguez  ;  William van der Touw  ;  Ana Jimenez  ;  Matthew Burns  ;  Jennifer Miller  ;  Manisha Brahmachary  ;  Hui-ming Chen  ;  Peter Boros  ;  Francisco Rausell-Palamos  ;  Tae Jin Yun  ;  Paloma Riquelme  ;  Alberto Rastrojo  ;  Begoña Aguado  ;  Joan Stein-Streilein  ;  Masato Tanaka  ;  Lan Zhou  ;  Junfeng Zhang  ;  Todd L. Lowary  ;  Florent Ginhoux  ;  Chae Gyu Park  ;  Cheolho Cheong  ;  Joshua Brody  ;  Shannon J. Turley  ;  Sergio A. Lira  ;  Vincenzo Bronte  ;  Siamon Gordon  ;  Peter S. Heeger  ;  Miriam Merad  ;  James Hutchinson 
Citation
 Immunity, Vol.42(6) : 1143-1158, 2015 
Journal Title
 Immunity 
ISSN
 1074-7613 
Issue Date
2015
Abstract
Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141259
DOI
10.1016/j.immuni.2015.05.009
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
박채규(Park, Chae Gyu)
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Full Text
http://www.sciencedirect.com/science/article/pii/S107476131500206X
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