CD300a immunoreceptor regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney

Nanako Nishiyama; Hitoshi Koizumi; Chigusa Nakahashi-Oda; Satoshi Fujiyama; Xuewei Ng; Hanbin Lee; Fumie Abe; Jinao Li; Yan Xu; Takehito Sugasawa; Kazuko Tajiri; Taketaro Sadahiro; Masaki Ieda; Keiji Tabuchi; Kazuko Shibuya; Akira Shibuya

doi:10.1172/JCI184984

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Nishiyama, N. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Koizumi, H. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

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¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Fujiyama, S. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Ng, X. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Lee, H. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Abe, F. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Li, J. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Xu, Y. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Sugasawa, T. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Tajiri, K. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Sadahiro, T. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Ieda, M. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Tabuchi, K. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Shibuya, K. in: PubMed | Google Scholar

¹Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

²Research and Development Group, TNAX Biopharma Corporation, Tsukuba, Japan

³Department of Sports Medicine Analysis, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁴Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan

⁵Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

⁶Department of Otolaryngology–Head and Neck Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan

⁷Department of Immunology, Institute of Medicine, University Of Tsukuba, Tsukuba, Japan

Find articles by Shibuya, A. in: PubMed | Google Scholar |

J Clin Invest. https://doi.org/10.1172/JCI184984.
Copyright © 2025, Nishiyama et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published July 24, 2025 - Version history

Acute ischemic organ diseases such as acute myocardial infarction and acute kidney injury often result in irreversible tissue damage and progress to chronic heart failure (CHF) and chronic kidney disease (CKD), respectively. However, the molecular mechanisms underlying the development of CHF and CKD remain incompletely understood. Here, we show that mice deficient in CD300a, an inhibitory immunoreceptor expressed on myeloid cells, showed enhanced efferocytosis by tissue-resident macrophages and decreased damage-associated molecular patterns and pathogenic SiglecF^hi neutrophils, resulting in milder inflammation-associated tissue injury than wild-type mice after ischemia and reperfusion (IR). Notably, we uncovered that CD300a-deficiency on SiglecF^lo neutrophils increased the signal transducer and activator of transcription 3-mediated production of pro-angiogenic and anti-fibrotic factors, resulting in milder adverse remodeling after IR. Our results demonstrated that CD300a plays an important role in the pathogenesis of ischemic tissue injury and adverse remodeling in the heart and kidney.

CD300a immunoreceptor regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney

Nanako Nishiyama,¹ Hitoshi Koizumi,¹ Chigusa Nakahashi-Oda,¹ Satoshi Fujiyama,¹ Xuewei Ng,¹ Hanbin Lee,¹ Fumie Abe,² Jinao Li,¹ Yan Xu,¹ Takehito Sugasawa,³ Kazuko Tajiri,⁴ Taketaro Sadahiro,⁵ Masaki Ieda,⁵ Keiji Tabuchi,⁶ Kazuko Shibuya,¹ and Akira Shibuya⁷

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CD300a immunoreceptor regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney

Nanako Nishiyama,1 Hitoshi Koizumi,1 Chigusa Nakahashi-Oda,1 Satoshi Fujiyama,1 Xuewei Ng,1 Hanbin Lee,1 Fumie Abe,2 Jinao Li,1 Yan Xu,1 Takehito Sugasawa,3 Kazuko Tajiri,4 Taketaro Sadahiro,5 Masaki Ieda,5 Keiji Tabuchi,6 Kazuko Shibuya,1 and Akira Shibuya7

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Nanako Nishiyama,¹ Hitoshi Koizumi,¹ Chigusa Nakahashi-Oda,¹ Satoshi Fujiyama,¹ Xuewei Ng,¹ Hanbin Lee,¹ Fumie Abe,² Jinao Li,¹ Yan Xu,¹ Takehito Sugasawa,³ Kazuko Tajiri,⁴ Taketaro Sadahiro,⁵ Masaki Ieda,⁵ Keiji Tabuchi,⁶ Kazuko Shibuya,¹ and Akira Shibuya⁷