Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.

Details

Serval ID
serval:BIB_A05555798EB8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Comte D., Karampetsou M.P., Kis-Toth K., Yoshida N., Bradley S.J., Mizui M., Kono M., Solomon J.R., Kyttaris V.C., Tsokos G.C.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
16/08/2016
Peer-reviewed
Oui
Volume
113
Number
33
Pages
9321-9326
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/function. Here we show that SLAMF3 functions as a costimulator on CD4(+) T cells and influences IL-2 response and T helper cell differentiation. SLAMF3 ligation promotes T-cell responses to IL-2 via up-regulation of CD25 in a small mothers against decapentaplegic homolog 3 (Smad3)-dependent mechanism. This augments the activation of the IL-2/IL-2R/STAT5 pathway and enhances cell proliferation in response to exogenous IL-2. SLAMF3 costimulation promotes Treg differentiation from naïve CD4(+) T cells. Ligation of SLAMF3 receptors on SLE CD4(+) T cells restores IL-2 responses to levels comparable to those seen in healthy controls and promotes functional Treg generation. Taken together, our results suggest that SLAMF3 acts as potential therapeutic target in SLE patients by augmenting sensitivity to IL-2.

Keywords
Adult, Aged, CD4-Positive T-Lymphocytes/drug effects, CD4-Positive T-Lymphocytes/immunology, Cell Differentiation, Cell Polarity, Female, Humans, Interleukin-2/biosynthesis, Interleukin-2/pharmacology, Interleukin-2 Receptor alpha Subunit/analysis, Interleukin-2 Receptor alpha Subunit/genetics, Lupus Erythematosus, Systemic/immunology, Male, Middle Aged, Signaling Lymphocytic Activation Molecule Family/physiology, T-Lymphocytes, Regulatory/physiology, IL-2, SLAMF3, SLE, Treg, autoimmunity
Pubmed
Web of science
Open Access
Yes
Create date
05/10/2016 10:54
Last modification date
20/08/2019 15:06
Usage data