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

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 to...

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Detalles Bibliográficos
Autores: Conde-San Román, Patricia, Rodriguez-Garcia, Mercedes, van der Touw, William, Jimenez, Ana, Burns, Matthew, Miller, Jennifer, Brahmachary, Manisha, Chen, Hui-ming, Boros, Peter, Rausell-Palamos, Francisco, Yun, Tae Jin, Riquelme, Paloma, Rastrojo, Alberto, Aguado, Begoña, Stein-Streilein, Joan, Tanaka, Masato, Zhou, Lan, Zhang, Junfeng, Lowary, Todd L, Ginhoux, Florent, Park, Chae Gyu, Cheong, Cheolho, Brody, Joshua, Turley, Shannon J, Lira, Sergio A, Bronte, Vincenzo, Gordon, Siamon, Heeger, Peter S, Merad, Miriam, Hutchinson, James, Chen, Shu-Hsia, Ochando, Jordi
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8565
Acceso en línea:http://hdl.handle.net/20.500.12105/8565
Access Level:acceso abierto
Palabra clave:Animals
CD8-Positive T-Lymphocytes
Cell Adhesion Molecules
Cells, Cultured
Forkhead Transcription Factors
Graft Rejection
Immune Tolerance
Interleukin-10
Lectins, C-Type
Macrophage Colony-Stimulating Factor
Macrophages
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Molecular Targeted Therapy
Receptors, Cell Surface
Light Signal Transduction
T-Lymphocytes, Regulatory
Toll-Like Receptor 4
Transplantation Tolerance
Up-Regulation
Heart Transplantation
Descripción
Sumario: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.

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