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
  • 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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