The Alternative NF-κB Pathway in Regulatory T Cell Homeostasis and Suppressive Function.

Autor:	Grinberg-Bleyer Y; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Caron R; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Seeley JJ; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., De Silva NS; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.; Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and.; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Schindler CW; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Hayden MS; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Klein U; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.; Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and.; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032., Ghosh S; Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; sg2715@columbia.edu.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Apr 01; Vol. 200 (7), pp. 2362-2371. Date of Electronic Publication: 2018 Feb 19.
DOI:	10.4049/jimmunol.1800042
Abstrakt:	CD4 + Foxp3 + regulatory T cells (Tregs) are essential regulators of immune responses. Perturbation of Treg homeostasis or function can lead to uncontrolled inflammation and autoimmunity. Therefore, understanding the molecular mechanisms involved in Treg biology remains an active area of investigation. It has been shown previously that the NF-κB family of transcription factors, in particular, the canonical pathway subunits, c-Rel and p65, are crucial for the development, maintenance, and function of Tregs. However, the role of the alternative NF-κB pathway components, p100 and RelB, in Treg biology remains unclear. In this article, we show that conditional deletion of the p100 gene, nfkb2 , in Tregs, resulted in massive inflammation because of impaired suppressive function of nfkb2 -deficient Tregs. Surprisingly, mice lacking RelB in Tregs did not exhibit the same phenotype. Instead, deletion of both relb and nfkb2 rescued the inflammatory phenotype, demonstrating an essential role for p100 as an inhibitor of RelB in Tregs. Our data therefore illustrate a new role for the alternative NF-κB signaling pathway in Tregs that has implications for the understanding of molecular pathways driving tolerance and immunity. (Copyright © 2018 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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