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Role of Prolactin in Promotion of Immune Cell Migration into the Mammary Gland

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Abstract

Immune cells in the mammary gland play a number of important roles, including protection against infection during lactation and, after passing into milk, modulation of offspring immunity. However, little is known about the mechanism of recruitment of immune cells to the lactating gland in the absence of infection. Given the importance of prolactin to other aspects of lactation, we hypothesized it would also play a role in immune cell recruitment. Prolactin treatment of adult female mice for a period equivalent to pregnancy and the first week of lactation increased immune cell flux through the mammary gland, as reflected in the number of immune cells in mammary gland-draining, but not other lymph nodes. Conditioned medium from luminal mammary epithelial HC11 cell cultures was chemo-attractive to CD4+ and CD8+ T cells, CD4+ and CD8+ memory T cells, B cells, macrophages, monocytes, eosinophils, and neutrophils. Prolactin did not act as a direct chemo-attractant, but through effects on luminal mammary epithelial cells, increased the chemo-attractant properties of conditioned medium. Macrophages and neutrophils constitute the largest proportion of cells in milk from healthy glands. Depletion of CCL2 and CXCL1 from conditioned medium reduced chemo-attraction of monocytes and neutrophils, and prolactin increased expression of these two chemokines in mammary epithelial cells. We conclude that prolactin is an important player in the recruitment of immune cells to the mammary gland both through its activities to increase epithelial cell number as well as production of chemo-attractants on a per cell basis.

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Acknowledgements

This work was supported by grants from National Institute of Child Health and Human Development # RO1-065099 and the California Breast Cancer Research Program # 171B-0053 to AMW. RD was also partially supported by Dorothy Pease and Burden fellowships. The authors thank Dr. Emma Wilson for access to the flow cytometer and Mary Y. Lorenson for provision of the prolactin and editorial assistance (both in the Division of Biomedical Sciences, University of California, Riverside).

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    Riva Dill & Ameae M. Walker

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Dill, R., Walker, A.M. Role of Prolactin in Promotion of Immune Cell Migration into the Mammary Gland. J Mammary Gland Biol Neoplasia 22, 13–26 (2017). https://doi.org/10.1007/s10911-016-9369-0

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