Title :

Growth Factor Midkine Promotes T-Cell Activation through Nuclear Factor of Activated T Cells Signaling and Th1 Cell Differentiation in Lupus Nephritis

Author(s) :

Masuda, Tomohiro [Auteur]
Nagoya University
Maeda, Kayaho [Auteur]
Nagoya University
Sato, Waichi [Auteur]
Nagoya University
Kosugi, Tomoki [Auteur]
Nagoya University
Sato, Yuka [Auteur]
Nagoya University
Kojima, Hiroshi [Auteur]
Nagoya University
Kato, Noritoshi [Auteur]
Nagoya University
Ishimoto, Takuji [Auteur]
Nagoya University
Tsuboi, Naotake [Auteur]
Nagoya University
Uchimura, Kenji [Auteur]
Nagoya University
Yuzawa, Yukio [Auteur]
Fujita Health University
Maruyama, Shoichi [Auteur]
Nagoya University
Kadomatsu, Kenji [Auteur]
Nagoya University

Journal title :

The American journal of pathology

Abbreviated title :

Am. J. Pathol.

Volume number :

187

Pages :

740-751

Publication date :

2017-04

ISSN :

1525-2191

English keyword(s) :

Spleen
Signal Transduction
Cytokines
T-Lymphocytes
Lymphocyte Activation
Intercellular Signaling Peptides and Proteins
Inflammation
NFATC Transcription Factors
Animals
Th1 Cells
Models, Biological
Lupus Nephritis
Mice
Cell Differentiation
Kidney Glomerulus

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for ...
Show more >Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk+/+) mice showed more severe glomerular injury than MK-deficient (Mdk-/-) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition. Compared with Mdk-/- mice, the frequency of splenic CD69+ T cells and T helper (Th) 1 cells, but not of regulatory T cells, was augmented in Mdk+/+ mice in proportion to LN disease activity, and was accompanied by skewed cytokine production. MK expression was also enhanced in activated CD4+ T cells in vivo and in vitro. MK induced activated CD4+ T cells expressing CD69 through nuclear activation of NFAT transcription and selectively increased in vitro differentiation of naive CD4+ T cells into Th1 cells by promoting IL-12/STAT4 signaling. These results suggest that MK serves an indispensable role in the NFAT-regulated activation of CD4+ T cells and Th1 cell differentiation, eventually leading to the exacerbation of LN.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Autres travaux scientifiques

Submission date :

2020-02-12T15:11:35Z
2021-03-18T09:38:59Z