TRAF3 regulates the effector function of regulatory T cells and humoral immune responses

Title
TRAF3 regulates the effector function of regulatory T cells and humoral immune responses
Author(s)
장재훈Shao-Cong Sun[Shao-Cong Sun]Hongbo Hu[Hongbo Hu]Jin Jin[Jin Jin]Nahum Puebla-Osorio[Nahum Puebla-Osorio]Yichuan Xiao[Yichuan Xiao]Brian E Gilbert[Brian E Gilbert]Robert Brink[Robert Brink]Stephen E Ullrich[Stephen E Ullrich]
Keywords
DEUBIQUITINATING ENZYME CYLD; RECEPTOR-ASSOCIATED FACTOR-3; GERMINAL CENTER; HELPER-CELLS; SURVIVAL SIGNALS; B-CELLS; DIFFERENTIATION; PREVENTS; HYPERMUTATION; AUTOIMMUNITY
Issue Date
201401
Publisher
ROCKEFELLER UNIV PRESS
Citation
JOURNAL OF EXPERIMENTAL MEDICINE, v.211, no.1, pp.137 - 151
Abstract
Regulatory T cells (T-reg cells) control different aspects of immune responses, but how the effector functions of T-reg cells are regulated is incompletely understood. Here we identified TNF receptor-associated factor 3 (TRAF3) as a regulator of T-reg cell function. T-reg cell-specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in T-reg cells resulted in increased antigen-stimulated activation of follicular T helper cells (T-FH cells), coupled with heightened formation of germinal centers and production of high-affinity IgG antibodies. Although the loss of TRAF3 did not reduce the overall frequency of T-reg cells, it attenuated the antigen-stimulated production of follicular T-reg cells (T-FR cells). TRAF3 signaling in T-reg cells was required to maintain high level expression of inducible co-stimulator (ICOS), which in turn was required for T-FR cell generation and inhibition of antibody responses. These findings establish TRAF3 as a mediator of T-reg cell function in the regulation of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in T-reg cells.
URI
http://hdl.handle.net/YU.REPOSITORY/33456http://dx.doi.org/10.1084/jem.20131019
ISSN
0022-1007
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약학대학 > 약학부 > Articles
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