Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

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

Abstract : 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.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-lille.fr/hal-03172990
Contributeur : Lilloa Université de Lille <>
Soumis le : jeudi 18 mars 2021 - 10:39:13
Dernière modification le : jeudi 18 mars 2021 - 10:39:14

Lien texte intégral

Identifiants

Collections

Citation

Tomohiro Masuda, Kayaho Maeda, Waichi Sato, Tomoki Kosugi, Yuka Sato, et al.. Growth Factor Midkine Promotes T-Cell Activation through Nuclear Factor of Activated T Cells Signaling and Th1 Cell Differentiation in Lupus Nephritis. The American journal of pathology, 2017, The American journal of pathology, 187 (4), pp.740-751. ⟨10.1016/j.ajpath.2016.12.006⟩. ⟨hal-03172990⟩

Partager

Métriques

Consultations de la notice

5