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A new therapeutic target: the CD69-Myl9 system in immune responses

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Abstract

CD69 is an activation marker on leukocytes. Early studies showed that the CD69+ cells were detected in the lung of patients with asthmatic and eosinophilic pneumonia, suggesting that CD69 might play crucial roles in the pathogenesis of such inflammatory diseases, rather than simply being an activation marker. Intensive studies using mouse models have since clarified that CD69 is a functional molecule regulating the immune responses. We discovered that Myosin light chain 9, 12a, 12b (Myl9/12) are ligands for CD69 and that platelet-derived Myl9 forms a net-like structure (Myl9 nets) that is strongly detected inside blood vessels in inflamed lung. CD69-expressing activated T cells attached to the Myl9 nets can thereby migrate into the inflamed tissues through a system known as the CD69-Myl9 system. In this review, we summarize the discovery of the CD69-Myl9 system and discuss how this system is important in inflammatory immune responses. In addition, we discuss our recent finding that CD69 controls the exhaustion status of tumor-infiltrating T cells and that the blockade of the CD69 function enhances anti-tumor immunity. Finally, we discuss the possibility of CD69 as a new therapeutic target for patients with intractable inflammatory disorders and tumors

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Acknowledgments

The authors acknowledge grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan: Grants-in Aid for Scientific Research (S) #26221305, (C) 18K07257, (C) 18K07165 and 17K15715, Grants-in Aid for Scientific Research on Innovative Areas #17H05787, Grants-in Aid for Challenging Research (Exploratory) #18K19466 and Practical Research Project for Allergic Diseases and Immunology from Japan Agency for Medical Research and Development (AMED) [JP18ek0410030], Project for Cancer Research and Therapeutic Evolution (P-CREATE) (AMED) [JP18cm0106339], Advanced Research & Development Programs for Medical Innovation, (AMED-CREST) (AMED) [JP18gm1210003].

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  1. Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Motoko Y. Kimura, Ryo Koyama-Nasu, Ryoji Yagi & Toshinori Nakayama

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Correspondence to Motoko Y. Kimura.

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T. Nakayama has received research fund from Genefrontier (Chiba, Japan). M.Y. Kimura, R. Koyama-Nasu, and R. Yagi declare that they have no conflict of interest.

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This article is a contribution to the special issue on The Pathogenicity of Acquired Immunity in Human Diseases - Guest Editor: Kiyoshi Hirahara

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Kimura, M.Y., Koyama-Nasu, R., Yagi, R. et al. A new therapeutic target: the CD69-Myl9 system in immune responses. Semin Immunopathol 41, 349–358 (2019). https://doi.org/10.1007/s00281-019-00734-7

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