Mucosal immunity in the female murine mammary gland

Courtney B. Betts, Nathan D. Pennock, Breanna P. Caruso, Brian Ruffell, Virginia F. Borges, Pepper Schedin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The mammary gland is not classically considered a mucosal organ, although it exhibits some features common to mucosal tissues. Notably, the mammary epithelium is contiguous with the external environment, is exposed to bacteria during lactation, and displays antimicrobial features. Nonetheless, immunological hallmarks predictive of mucosal function have not been demonstrated in the mammary gland, including immune tolerance to foreign Ags under homeostasis. This inquiry is important, as mucosal immunity in the mammary gland may assure infant and women’s health during lactation. Further, such mucosal immune programs may protect mammary function at the expense of breast cancer promotion via decreased immune surveillance. In this study, using murine models, we evaluated mammary specific mucosal attributes focusing on two reproductive states at increased risk for foreign and self-antigen exposure: lactation and weaning-induced involution. We find a baseline mucosal program of RORgT+ CD4+ T cells that is elevated within lactating and involuting mammary glands and is extended during involution to include tolerogenic dendritic cell phenotypes, barrier-supportive antimicrobials, and immunosuppressive Foxp3+ CD4+ T cells. Further, we demonstrate suppression of Ag-dependent CD4+ T cell activation, data consistent with immune tolerance. We also find Ag-independent accumulation of memory RORgT+ Foxp3+ CD4+ T cells specifically within the involution mammary gland consistent with an active immune process. Overall, these data elucidate strong mucosal immune programs within lactating and involuting mammary glands. Our findings support the classification of the mammary gland as a temporal mucosal organ and open new avenues for exploration into breast pathologic conditions, including compromised lactation and breast cancer.

Original languageEnglish (US)
Pages (from-to)734-746
Number of pages13
JournalJournal of Immunology
Volume201
Issue number2
DOIs
StatePublished - Jul 15 2018

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Mucosal Immunity
Human Mammary Glands
Lactation
Breast
T-Lymphocytes
Immune Tolerance
Breast Neoplasms
Autoantigens
Women's Health
Immunosuppressive Agents
Weaning
Dendritic Cells
Mucous Membrane
Homeostasis
Epithelium
Bacteria
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Betts, C. B., Pennock, N. D., Caruso, B. P., Ruffell, B., Borges, V. F., & Schedin, P. (2018). Mucosal immunity in the female murine mammary gland. Journal of Immunology, 201(2), 734-746. https://doi.org/10.4049/jimmunol.1800023

Mucosal immunity in the female murine mammary gland. / Betts, Courtney B.; Pennock, Nathan D.; Caruso, Breanna P.; Ruffell, Brian; Borges, Virginia F.; Schedin, Pepper.

In: Journal of Immunology, Vol. 201, No. 2, 15.07.2018, p. 734-746.

Research output: Contribution to journalArticle

Betts, CB, Pennock, ND, Caruso, BP, Ruffell, B, Borges, VF & Schedin, P 2018, 'Mucosal immunity in the female murine mammary gland', Journal of Immunology, vol. 201, no. 2, pp. 734-746. https://doi.org/10.4049/jimmunol.1800023
Betts CB, Pennock ND, Caruso BP, Ruffell B, Borges VF, Schedin P. Mucosal immunity in the female murine mammary gland. Journal of Immunology. 2018 Jul 15;201(2):734-746. https://doi.org/10.4049/jimmunol.1800023
Betts, Courtney B. ; Pennock, Nathan D. ; Caruso, Breanna P. ; Ruffell, Brian ; Borges, Virginia F. ; Schedin, Pepper. / Mucosal immunity in the female murine mammary gland. In: Journal of Immunology. 2018 ; Vol. 201, No. 2. pp. 734-746.
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