CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment

Autor: Hilary J. Selden, Anna G. Sorace, Adrian Liston, Lauren I.R. Ehrlich, Annemarie van Nieuwenhuijze, Yu Li, Angela M. Jarrett, Zicheng Hu, Thomas E. Yankeelov
Rok vydání: 2017
Předmět:
0301 basic medicine
Receptors
CCR7
Cell Survival
Apoptosis
chemical and pharmacologic phenomena
C-C chemokine receptor type 7
Thymus Gland
Biology
Lymphocyte Activation
T-Lymphocytes
Regulatory
Article
General Biochemistry
Genetics and Molecular Biology
Mice
03 medical and health sciences
Negative selection
thymus
immune system diseases
Immune Tolerance
Animals
Compartment (development)
Receptors
Immunologic
lcsh:QH301-705.5
thymocyte development
Bone Marrow Transplantation
central tolerance
Mice
Knockout
Transplantation Chimera
Thymocytes
chemokine receptor
Cell Differentiation
hemic and immune systems
Dendritic Cells
Dendritic cell
biological factors
Cell biology
Mice
Inbred C57BL
Tolerance induction
Haematopoiesis
regulatory T cells
030104 developmental biology
lcsh:Biology (General)
Gene Expression Regulation
Immunology
tissues
Whole-Body Irradiation
Function (biology)
CCR7
Signal Transduction
Zdroj: Cell Reports, Vol 21, Iss 1, Pp 168-180 (2017)
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.09.016
Popis: Upon recognition of auto-antigens, thymocytes are negatively selected or diverted to a regulatory T cell (Treg) fate. CCR7 is required for negative selection of auto-reactive thymocytes in the thymic medulla. Here, we describe an unanticipated contribution of CCR7 to intrathymic Treg generation. Ccr7(-/-) mice have increased Treg cellularity because of a hematopoietic but non-T cell autonomous CCR7 function. CCR7 expression by thymic dendritic cells (DCs) promotes survival of mature Sirpα(-) DCs. Thus, CCR7 deficiency results in apoptosis of Sirpα(-) DCs, which is counterbalanced by expansion of immature Sirpα(+) DCs that efficiently induce Treg generation. CCR7 deficiency results in enhanced intrathymic generation of Tregs at the neonatal stage and in lymphopenic adults, when Treg differentiation is critical for establishing self-tolerance. Together, these results reveal a complex function for CCR7 in thymic tolerance induction, where CCR7 not only promotes negative selection but also governs intrathymic Treg generation via non-thymocyte intrinsic mechanisms. ispartof: Cell Reports vol:21 issue:1 pages:168-180 ispartof: location:United States status: published
Databáze: OpenAIRE
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