Identification and characterization of the secreted form of TMEM98 that promotes Th1 cell differentiation both in vitro and in vivo.
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1
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; Peking University Center for Human Disease Genomics; Key Laboratory of Medical Immunology, Ministry of Health, China
Cytokines are secreted proteins that mediate the communication among immune cells. They play critical roles in the differentiation and effector function of CD4+ T cells. More importantly, cytokines have made effective targets for drug development for a variety of diseases. Therefore, identifying novel potential cytokines will be of great value. We have established an immunogenomic platform to identify secreted proteins with modulatory effects on immune cells. In this study, we demonstrate that TMEM98 is a type II transmembrane protein that is secreted by a non-classical pathway. GEO profile analysis indicated that TMEM98 might be involved in anti-viral and anti-tumor immunity. We found that mouse CD4+ T cells upregulated TMEM98 upon stimulation, especially on activated Th1 cells. When placed under Th1-skewing conditions, recombinant TMEM98 could increase both the percentage of IFN-γ+ cells and IFN-γ secretion into culture medium. Moreover, T-bet expression, the key Th1 transcription factor, was also upregulated. These findings were confirmed in vivo, as recombinant TMEM98 administration significantly increased antigen-specific IFN-γ production and serum antigen-specific IgG2a in the mBSA-induced delayed-type hypersensitivity (DTH) model. Overall, these observations emphasize an essential role of TMEM98 in promoting Th1 cell differentiation, thereby adding to the understanding of Th1 cell development.
Acknowledgements
This work was supported by grants from the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110001110016) and the Program for Innovation of New Drugs (2013ZX09103003-023).
Keywords:
immunogenomics,
cytokine,
TMEM98,
Th1 Cells,
Delayed-type hypersensitivity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Fu
W,
Zhang
Y,
Cheng
Y,
Wang
P,
Li
T,
Pan
W,
Ma
D and
Han
W
(2013). Identification and characterization of the secreted form of TMEM98 that promotes Th1 cell differentiation both in vitro and in vivo..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00358
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Received:
18 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Wenling Han, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; Peking University Center for Human Disease Genomics; Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China, hanwl@bjmu.edu.cn