Impaired T-cell activation in patients with systemic lupus erythematosus

1989 ◽  
Vol 9 (6) ◽  
pp. 469-476 ◽  
Author(s):  
Stanislaw Sierakowski ◽  
Eugene J. Kucharz ◽  
Robert W. Lightfoot ◽  
James S. Goodwin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus

scholarly journals Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

2015 ◽  
Vol 182 (1) ◽  
pp. 1-13 ◽  
Author(s):  
J. P. Mackern-Oberti ◽  
J. Obreque ◽  
G. P. Méndez ◽  
C. Llanos ◽  
A. M. Kalergis
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Carbon Monoxide ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus ◽  
Target Organs

scholarly journals MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1433 ◽  
Author(s):  
Chuang ◽  
Tan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Therapeutic Targets ◽  
T Cell Signaling ◽  
Systemic Lupus

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE.

scholarly journals Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus

2012 ◽  
Vol 64 (9) ◽  
pp. 2953-2963 ◽  
Author(s):  
Shu Ding ◽  
Yunsheng Liang ◽  
Ming Zhao ◽  
Gongping Liang ◽  
Hai Long ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Systemic Lupus

scholarly journals Defective CD2 pathway T cell activation in systemic lupus erythematosus

1991 ◽  
Vol 34 (5) ◽  
pp. 561-571 ◽  
Author(s):  
David A. Fox ◽  
Jo Ann Millard ◽  
Jonathan Treisman ◽  
Wendy Zeldes ◽  
Alice Bergman ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus

scholarly journals Glucose Oxidation Is Critical for CD4+ T Cell Activation in a Mouse Model of Systemic Lupus Erythematosus

2015 ◽  
Vol 196 (1) ◽  
pp. 80-90 ◽  
Author(s):  
Yiming Yin ◽  
Seung-Chul Choi ◽  
Zhiwei Xu ◽  
Leilani Zeumer ◽  
Nathalie Kanda ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Mouse Model ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Glucose Oxidation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Systemic Lupus

scholarly journals T-cell activation, alterations in systemic lupus erythematosus: A narrative review

2018 ◽  
Vol 25 (1) ◽  
pp. 38-54
Author(s):  
C. Nicolás Téllez ◽  
José J. Siachoque ◽  
S. Juan Siachoque ◽  
J. María Alejandra Siachoque ◽  
M. Heber Siachoque
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Narrative Review ◽  
Systemic Lupus

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

2016 ◽  
Vol 113 (33) ◽  
pp. 9321-9326 ◽  
Author(s):  
Denis Comte ◽  
Maria P. Karampetsou ◽  
Katalin Kis-Toth ◽  
Nobuya Yoshida ◽  
Sean J. Bradley ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Regulatory T Cell ◽  
Cell Activation ◽  
Cell Polarization ◽  
Systemic Lupus ◽  
Signaling Lymphocytic Activation Molecule

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.

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