z-logo
Premium
Cystatin C regulates major histocompatibility complex‐ II –peptide presentation and extracellular signal‐regulated kinase‐dependent polarizing cytokine production by bone marrow‐derived dendritic cells
Author(s) -
Zhang Wenjie,
Zi Mengting,
Sun Li,
Wang Fengge,
Chen Shun,
Zhao Yanfang,
Liang Shuangchao,
Hu Jiqiong,
Liu Shan,
Liu Lei,
Zhan Yifan,
Lew Andrew M,
Xu Yuekang
Publication year - 2019
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12290
Subject(s) - proteases , cystatin , cystatin c , microbiology and biotechnology , immune system , biology , major histocompatibility complex , cytokine , antigen presentation , proinflammatory cytokine , t cell , immunology , biochemistry , inflammation , enzyme , renal function
Cystatin C is a ubiquitously expressed cysteine protease inhibitor that protects cells from either improper hydrolysis by endogenous proteases or pathogen growth/virulence by exogenous proteases. Although commonly used as a serum biomarker for evaluating renal function, cystatin C is associated with many immunological disorders under various pathophysiological conditions. How cystatin C affects immune cells, especially dendritic cells ( DC s), however, is far from clear. In this study, we found that pharmacological treatment with or genetic overexpression of cystatin C in bone marrow‐derived DC s ( BMDC s) reduced their capacity to stimulate CD 4 + T‐cell proliferation, despite increased antigen uptake. This reduced capacity corresponded with reduced major histocompatibility complex‐II presentation owing to diminished levels of the chaperon H2‐ DM in BMDC s. Instead of promoting proliferation, cystatin C promoted skewing of T cells toward proinflammatory T‐helper (Th)1/Th17 differentiation. This was mediated by augmented extracellular signal‐regulated kinase 1/2 mitogen‐activated protein kinase phosphorylation in BMDC s, leading to secretion of polarizing cytokines, which in turn led to the Th deviation. Collectively, our study explained the cellular and molecular basis of how this protease inhibitor can regulate immune responses, namely by affecting BMDC s and their cytokine pathway. Our results might open up an avenue for the development of therapeutic agents for the treatment of cystatin C‐related immunological diseases.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here