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oai:repisalud.isciii.es:20.500.12105/85652024-09-27T23:23:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Conde-San Román, Patricia author Rodriguez-Garcia, Mercedes author van der Touw, William author Jimenez, Ana author Burns, Matthew author Miller, Jennifer author Brahmachary, Manisha author Chen, Hui-ming author Boros, Peter author Rausell-Palamos, Francisco author Yun, Tae Jin author Riquelme, Paloma author Rastrojo, Alberto author Aguado, Begoña author Stein-Streilein, Joan author Tanaka, Masato author Zhou, Lan author Zhang, Junfeng author Lowary, Todd L author Ginhoux, Florent author Park, Chae Gyu author Cheong, Cheolho author Brody, Joshua author Turley, Shannon J author Lira, Sergio A author Bronte, Vincenzo author Gordon, Siamon author Heeger, Peter S author Merad, Miriam author Hutchinson, James author Chen, Shu-Hsia author Ochando, Jordi author 2015-06-16 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. Immunity. 2015 Jun 16;42(6):1143-58. 10.1016/j.immuni.2015.05.009 1097-4180 1074-7613 Immunity 26070485 http://hdl.handle.net/20.500.12105/8565 DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance