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Reverse signaling using an inducible costimulator to enhance immunogenic function of dendritic cells

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Abstract

A costimulatory signal from an inducible costimulator (ICOS) of T cells plays a critical role in immunological homeostasis. This study shows that the interaction of ICOSIg and its ligand (ICOSL) on mouse bone marrow-derived dendritic cells (DCs) induces a p38-MAPK dependent elevation of interleukin 6 (IL-6). It also enhances phagocytosis and the antigen-presentation function of DCs in vitro, further favoring cell-mediated immunity in vivo. As seen for other types of costimulator molecules expressed in the T cells in the CD28 family, it is shown here for the first time that ICOS can also deliver reverse signals through its ligand to ICOSL-expressing cells. These reverse signals in turn transfer positive immunogenic information to bone marrow-derived DCs. Our work therefore provides new recognition of an ICOSL/ICOS signal pathway in immunity and also supplies more evidence that this ICOSL/ICOS signal pathway is a reasonable target for therapeutic drugs.

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Acknowledgments

We would like take the opportunity to thank Professor Xuetao Cao for kindly providing us with OVA-transgene mouse (DO11.10) and Doctor Liwei Dong for SB202190, an inhibitor of p38 MPAK pathway, and its inactive analog, SB202474. The authors declare that there were no financial interest conflicts raised during this study.

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Authors and Affiliations

  1. Department of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University, Room 701, Building of Laboratory Medicine and Technology, Number 168, Changhai Road, 200433, Shanghai, China

    Gusheng Tang, Qin Qin, Peng Zhang, Menglei Liu, Qingli Ding, Yanghua Qin & Qian Shen

  2. Department of Respiratory Medicine, Changzheng Hospital, The Second Military Medical University, Number 415, Fengyang Road, 200433, Shanghai, China

    Guifang Wang

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  1. Gusheng Tang
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Correspondence to Qian Shen.

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Tang, G., Qin, Q., Zhang, P. et al. Reverse signaling using an inducible costimulator to enhance immunogenic function of dendritic cells. Cell. Mol. Life Sci. 66, 3067–3080 (2009). https://doi.org/10.1007/s00018-009-0090-7

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