CD47 promotes peripheral T cell survival by preventing dendritic cell–mediated T cell necroptosis

Author:

Komori Satomi12ORCID,Saito Yasuyuki2ORCID,Nishimura Taichi2,Respatika Datu23,Endoh Hiromi4,Yoshida Hiroki2,Sugihara Risa2ORCID,Iida-Norita Rie2ORCID,Afroj Tania12ORCID,Takai Tomoko12,Oduori Okechi S.12ORCID,Nitta Eriko4,Kotani Takenori2ORCID,Murata Yoji2ORCID,Kaneko Yoriaki5,Nitta Ryo4ORCID,Ohnishi Hiroshi6ORCID,Matozaki Takashi12ORCID

Affiliation:

1. Division of Biosignal Regulation, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan

2. Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

3. Division of Reconstruction, Oculoplasty, and Oncology, Department of Ophthalmology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University, Yogyakarta 55281, Indonesia

4. Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

5. Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan

6. Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma 371-8514, Japan

Abstract

Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell–specific CD47-deficient ( Cd47  ΔT ) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47   ΔT mice required expression of its receptor signal regulatory protein α on cDCs. The development of CD4 + T helper cell–dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8 + T cells were both markedly impaired in Cd47  ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.

Funder

MEXT | Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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