Ets1 Controls the Development of B Cell Autoimmune Responses in a Cell-Intrinsic Manner.

Autor: Sunshine A; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Goich D; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Stith A; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Sortino K; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Dalton J; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Metcalfe S; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and., Svensson EC; Division of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637., Garrett-Sinha LA; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203; and leesinha@buffalo.edu.
Jazyk: angličtina
Zdroj: ImmunoHorizons [Immunohorizons] 2019 Jul 17; Vol. 3 (7), pp. 331-340. Date of Electronic Publication: 2019 Jul 17.
DOI: 10.4049/immunohorizons.1900033
Abstrakt: Ets1 is emerging as a key transcription factor that is required to prevent autoimmunity in mice and humans. Ets1 is expressed in both B and T cells, and mice lacking Ets1 are characterized by excess B and T cell activation, leading to enhanced formation of Ab-secreting cells and high titers of autoantibodies. In humans, genome-wide association studies have detected associations of single nucleotide polymorphisms in the human ETS1 gene with autoimmune diseases, including lupus. An increased fraction of CD4 + T cells from Ets1 -/- mice have an activated effector-memory phenotype, and there are aberrations in differentiation that contribute to the autoimmune phenotype. In vitro studies of B cells suggest that Ets1 may have B cell-intrinsic effects as well. To confirm B cell-intrinsic roles for Ets1, we crossed CD19-Cre mice to mice with a floxed allele of Ets1. Mice with a B cell-specific deletion of Ets1 show increases in B cell activation, numbers of Ab-secreting cells, and levels of autoantibodies, despite the fact that T cells are normal. However, when compared with conventional Ets1 knockout mice, mice with B cell-specific loss of Ets1 have a significantly milder phenotype. These results demonstrate that Ets1 is required in B cells to prevent autoimmune responses but that loss of Ets1 activity in other cell types is required for maximal autoimmune phenotypes.
(Copyright © 2019 The Authors.)
Databáze: MEDLINE