Jaquish Abigail, Phung Eleni, Gong Xutong, Baldominos Pilar, Galván-Peña Silvia, Magill Ian, Bursulaya Isabelle, Marina Eleonora, Bertrand Kerri, Chambers Christina, Muñoz-Rojas Andrés R, Agudo Judith, Mathis Diane, Benoist Christophe, Ramanan Deepshika
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Nat Immunol. 2025 Aug;26(8):1411-1422. doi: 10.1038/s41590-025-02218-3. Epub 2025 Jul 29.
Pregnancy brings about profound changes in the mammary gland to prepare for lactation, yet immunocyte changes that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells, revealing a marked increase in CD4 and CD8 T effector cells, including an expansion of T cell receptor (TCR)αβCD8αα cells, in pregnancy and lactation. T cells were localized in the mammary epithelium, resembling intraepithelial lymphocytes (IELs) typically found in mucosal tissues. Similarity to mucosal tissues was substantiated by demonstrating partial dependence on microbial cues, T cell migration from the intestine to the mammary gland in late pregnancy and shared TCR clonotypes between intestinal and mammary tissues, including intriguing public TCR families. Putative counterparts of mammary IELs were found in human breast and milk. Mammary IELs are thus poised to manage the transition from a nonmucosal tissue to a mucosal barrier during lactogenesis.
怀孕会使乳腺发生深刻变化以准备泌乳，但伴随这种快速重塑的免疫细胞变化尚未完全明了。我们全面分析了乳腺T细胞，发现妊娠和哺乳期CD4和CD8 T效应细胞显著增加，包括T细胞受体（TCR）αβCD8αα细胞的扩增。T细胞定位于乳腺上皮，类似于通常在黏膜组织中发现的上皮内淋巴细胞（IEL）。通过证明部分依赖微生物信号、妊娠晚期T细胞从肠道迁移至乳腺以及肠道和乳腺组织之间共享TCR克隆型（包括有趣的公共TCR家族），证实了与黏膜组织的相似性。在人类乳房和乳汁中发现了乳腺IEL的假定对应物。因此，乳腺IEL准备好在泌乳过程中管理从非黏膜组织到黏膜屏障的转变。
