Growth Factor Midkine Promotes T-Cell ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Growth Factor Midkine Promotes T-Cell Activation through Nuclear Factor of Activated T Cells Signaling and Th1 Cell Differentiation in Lupus Nephritis
Auteur(s) :
Masuda, Tomohiro [Auteur]
Maeda, Kayaho [Auteur]
Sato, Waichi [Auteur]
Kosugi, Tomoki [Auteur]
Sato, Yuka [Auteur]
Kojima, Hiroshi [Auteur]
Kato, Noritoshi [Auteur]
Ishimoto, Takuji [Auteur]
Tsuboi, Naotake [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Yuzawa, Yukio [Auteur]
Maruyama, Shoichi [Auteur]
Kadomatsu, Kenji [Auteur]
Maeda, Kayaho [Auteur]
Sato, Waichi [Auteur]
Kosugi, Tomoki [Auteur]
Sato, Yuka [Auteur]
Kojima, Hiroshi [Auteur]
Kato, Noritoshi [Auteur]
Ishimoto, Takuji [Auteur]
Tsuboi, Naotake [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Yuzawa, Yukio [Auteur]
Maruyama, Shoichi [Auteur]
Kadomatsu, Kenji [Auteur]
Titre de la revue :
The American journal of pathology
Nom court de la revue :
Am. J. Pathol.
Numéro :
187
Pagination :
740-751
Date de publication :
2017-04
ISSN :
1525-2191
Mot(s)-clé(s) en anglais :
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
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
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Langue :
Anglais
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Date de dépôt :
2020-02-12T15:11:35Z