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<p>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<sup>+</sup> and CD8<sup>+</sup> T effector cells, including an expansion of T cell receptor (TCR)αβ<sup>+</sup>CD8αα<sup>+</sup> 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.</p>

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Mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis

  • 期刊论文

  • 发表日期：

    2025年7月29日

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  • Abigail Jaquish,
  • Eleni Phung,
  • Xutong Gong,
  • Pilar Baldominos,
  • Silvia Galván-Peña,
  • Ian Magill,
  • Isabelle Bursulaya,
  • Eleonora Marina,
  • Aaron Liu,
  • Alexander Chervonsky,
  • Alexandra Cassano,
  • Alia Welsh,
  • Ananda Goldrath,
  • Andrea Lebron-Figueroa,
  • Ankit Malik,
  • Anna-Maria Globig,
  • Antoine Freuchet,
  • Bana Jabri,
  • Charlotte Imianowski,
  • Claire Thefane,
  • Dan Kaplan,
  • Dania Mallah,
  • Dario Vignali,
  • David Sinclair,
  • David Zemmour,
  • Derek Bangs,
  • Domenic Abbondanza,
  • Enxhi Ferraj,
  • Eric Weiss,
  • Erin Lucas,
  • Evelyn Chang,
  • Gavyn Bee,
  • Giovanni Galleti,
  • Iliyan Iliev,
  • Jinseok Park,
  • Joonsoo Kang,
  • Jordan Voisine,
  • Josh Choi,
  • Julia Merkenschlager,
  • Jun Huh,
  • Katharine Block,
  • Ken Cadwell,
  • Kevin Osum,
  • Laurent Brossay,
  • Laurent Gapin,
  • Liang Yang,
  • Lizzie Garcia-Rivera,
  • Marc Jenkins,
  • Maria Brbic,
  • Marion Pepper,
  • Marisa Alegre,
  • Mariya London,
  • Matthew Stephens,
  • Maurizio Fiusco,
  • Melanie Vacchio,
  • Michael Starnbach,
  • Michel Nussenzweig,
  • Mitchell Kronenberg,
  • Myriam Croze,
  • Nalat Siwapornchai,
  • Nathan Morris,
  • Nika Abdollahi,
  • Niket Patel,
  • Odhran Casey,
  • Olga Barreiro,
  • Paul Thomas,
  • Peter Carbonetto,
  • Remy Bosselut,
  • Rocky Lai,
  • Sam Behar,
  • Sam Borys,
  • Sara Quon,
  • Serge Candéias,
  • Shanelle Reilly,
  • Shanshan Zhang,
  • Siba Smarak Panigrahi,
  • Sofia Kossida,
  • Stefan Muljo,
  • Stefan Schattgen,
  • Stefani Spranger,
  • Steve Jameson,
  • Susan Kaech,
  • Takato Kusakabe,
  • Taylor Heim,
  • Tianze Wang,
  • Tomoyo Shinkawa,
  • Ulrich von Andrian,
  • Val Piekarsa,
  • Véronique Giuducelli,
  • Vijay Kuchroo,
  • Woan-Yu Lin,
  • Kerri Bertrand,
  • Christina Chambers,
  • Andrés R. Muñoz-Rojas,
  • Judith Agudo,
  • Diane Mathis,
  • Christophe Benoist,
  • Deepshika Ramanan

摘要

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)αβ+CD8αα+ 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.