2. Academic Validation
  3. Identification of endometrial CD169+ macrophages essential for Treg cell accumulation and implantation

Identification of endometrial CD169+ macrophages essential for Treg cell accumulation and implantation

  • Cell Rep. 2026 Mar 24;45(3):117040. doi: 10.1016/j.celrep.2026.117040.
Takuto Ohki 1,  Shingo Miyawaki 2,  Tsunaki Higa 3,  Hiroki Yamazaki 4,  Hiromu Okaki 5,  Ryusuke Nakajima 6,  Kai Kitamura 6,  Megumi G Nakagawa 6,  Tsukasa Sanosaka 7,  Hitoshi Tsugawa 8,  Kurara Honda 9,  Akihiro Hirata 6,  Takeshi Goto 5,  Mika Handa 5,  Katsuhiro Tokutake 10,  Sota Saeki 10,  Michiro Yamamoto 10,  Kazuhiro Watanabe 11,  Sadatoshi Maeda 11,  Masaki Takasu 12,  Yuki Sugiura 13,  Tsuyoshi Takiuchi 14,  Jun Kohyama 15,  Makoto Suematsu 16,  Hitoshi Hirata 10
Affiliations

Affiliations

  • 1 Department of Human Enhancement and Hand Surgery, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan; Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: [email protected].
  • 2 Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu 501-1193, Japan. Electronic address: [email protected].
  • 3 Anticancer Strategies Laboratory, Advanced Research Initiative, Institute of Science Tokyo, Tokyo 113-8510, Japan.
  • 4 Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
  • 5 Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Osaka, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 6 Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan.
  • 7 Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
  • 8 Transkingdom Signaling Research Unit, Division of Host Defense Mechanism, Tokai University School of Medicine, Isehara 259-1193, Japan.
  • 9 Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
  • 10 Department of Human Enhancement and Hand Surgery, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan.
  • 11 Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu 501-1193, Japan.
  • 12 Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu 501-1193, Japan; Institute for Advanced Study, Gifu University, Gifu 501-1193, Japan; Department of Developmental and Reproductive Engineering, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Kita, Okayama 700-8558, Japan.
  • 13 Center for Cancer Immunotherapy and Immunobiology, Multi-Omics Platform, Graduate School of Medicine, Kyoto University, Kyoto 606-8315, Japan.
  • 14 Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Osaka, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Clinical Genomics, Graduate School of Medicine, The University of Osaka, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 15 Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Laboratory of Stem Cell Biology, Faculty of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
  • 16 Central Institute for Experimental Medicine and Life Science, Kawasaki, Kanagawa 210-0821, Japan; AMED SCARDA Support Core Group, Minato-ku, Tokyo, Japan.
PMID: 41712382 DOI: 10.1016/j.celrep.2026.117040
Abstract

Successful pregnancy requires coordinated regulation between the innate and adaptive immune systems. Regulatory T (Treg) cells are essential for establishing maternal immune tolerance to the semi-allogeneic fetus, but the innate immune cells that modulate this process remain poorly defined. Here, we identify CD169+ macrophages in the endometrium as critical regulators of Treg cell recruitment and implantation. These CD169+ macrophages are endometrial localized, exhibit an anti-inflammatory phenotype, and secrete chemokines that attract Treg cells to the endometrium. We also identified CD169+ macrophages in the human endometrium that express chemokines involved in Treg cell recruitment. Our findings identify endometrial CD169+ macrophages as key orchestrators of Treg cell accumulation at the maternal-fetal interface, providing mechanistic insight into implantation and conceptus development.

Keywords

CD169(+) macrophages; CP: Immunology; chemokines; immune tolerance; pregnancy; regulatory T cells.

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