Skip to main content

Advertisement

SpringerLink
Log in

Immune Cell Location and Function During Post-Natal Mammary Gland Development

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

Abbreviations

TGFβ:

Transforming growth factor β

TNFα:

Tumor necrosis factor α

IL:

Interleukin

PMN:

Polymorphonuclear leukocytes

TGFα:

Transforming growth factor α

EGF:

Epidermal growth factor

Th1:

T helper cell 1

Th2:

T helper cell 2

IFNγ:

Interferon-γ

TEB:

Terminal end bud

CLA:

Conjugated linoleic acid

Csf1:

Colony-stimulating factor 1

MMTV:

Mouse mammary tumor virus

Tg:

Transgenic

NGF:

Nerve growth factor

CSF-1R:

Colony stimulating factor 1 receptor

IgA:

Immunoglobulin A

VCAM-1:

Vascular cell adhesion molecule-1

References

  1. Watson CJ, Khaled WT. Mammary development in the embryo and adult: a journey of morphogenesis and commitment. Development. 2008;135(6):995–1003.

    Article  CAS  PubMed  Google Scholar 

  2. Regan MC, Kirk SJ, Wasserkrug HL, Barbul A. The wound environment as a regulator of fibroblast phenotype. J Surg Res. 1991;50(5):442–8.

    Article  CAS  PubMed  Google Scholar 

  3. Adamson R. Role of macrophages in normal wound healing: an overview. J Wound Care. 2009;18(8):349–51.

    CAS  PubMed  Google Scholar 

  4. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585–601.

    Article  PubMed  Google Scholar 

  5. Glaros T, Larsen M, Li L. Macrophages and fibroblasts during inflammation, tissue damage and organ injury. Front Biosci. 2009;14:3988–93.

    Article  CAS  PubMed  Google Scholar 

  6. Park JE, Barbul A. Understanding the role of immune regulation in wound healing. Am J Surg. 2004;187(5A):11S–6S.

    Article  CAS  PubMed  Google Scholar 

  7. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–86.

    Article  CAS  PubMed  Google Scholar 

  8. Mantovani A, Allavena P, Sica A. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur J Cancer. 2004;40(11):1660–7.

    Article  CAS  PubMed  Google Scholar 

  9. Allavena P, Sica A, Garlanda C, Mantovani A. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev. 2008;222:155–61.

    Article  CAS  PubMed  Google Scholar 

  10. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005;6(12):1191–7.

    Article  CAS  PubMed  Google Scholar 

  11. Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S73–80.

    PubMed  Google Scholar 

  12. Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010;10(6):440–52.

    Article  CAS  PubMed  Google Scholar 

  13. Chen R, Ning G, Zhao ML, Fleming MG, Diaz LA, Werb Z, et al. Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid. J Clin Invest. 2001;108(8):1151–8.

    CAS  PubMed  Google Scholar 

  14. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147–74.

    Article  CAS  PubMed  Google Scholar 

  15. Kouro T, Takatsu K. IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol. 2009;21(12):1303–9.

    Article  CAS  PubMed  Google Scholar 

  16. Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med. 1995;182(4):1169–74.

    Article  CAS  PubMed  Google Scholar 

  17. Mould AW, Matthaei KI, Young IG, Foster PS. Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice. J Clin Invest. 1997;99(5):1064–71.

    Article  CAS  PubMed  Google Scholar 

  18. Rothenberg ME. Eotaxin. An essential mediator of eosinophil trafficking into mucosal tissues. Am J Respir Cell Mol Biol. 1999;21(3):291–5.

    CAS  PubMed  Google Scholar 

  19. Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood. 1992;79(12):3101–9.

    CAS  PubMed  Google Scholar 

  20. Sferruzzi-Perri AN, Robertson SA, Dent LA. Interleukin-5 transgene expression and eosinophilia are associated with retarded mammary gland development in mice. Biol Reprod. 2003;69(1):224–33.

    Article  CAS  PubMed  Google Scholar 

  21. Ohno I, Lea RG, Flanders KC, Clark DA, Banwatt D, Dolovich J, et al. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest. 1992;89(5):1662–8.

    Article  CAS  PubMed  Google Scholar 

  22. Todd R, Donoff BR, Chiang T, Chou MY, Elovic A, Gallagher GT, et al. The eosinophil as a cellular source of transforming growth factor alpha in healing cutaneous wounds. Am J Pathol. 1991;138(6):1307–13.

    CAS  PubMed  Google Scholar 

  23. Teller P, White TK. The physiology of wound healing: injury through maturation. Surg Clin North Am. 2009;89(3):599–610.

    Article  PubMed  Google Scholar 

  24. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development. 2000;127(11):2269–82.

    CAS  PubMed  Google Scholar 

  25. Lilla JN, Werb Z. Mast cells contribute to the stromal microenvironment in mammary gland branching morphogenesis. Dev Biol. 2010;337(1):124–33.

    Article  CAS  PubMed  Google Scholar 

  26. Pollard JW, Hennighausen L. Colony stimulating factor 1 is required for mammary gland development during pregnancy. Proc Natl Acad Sci U S A. 1994;91(20):9312–6.

    Article  CAS  PubMed  Google Scholar 

  27. Bourges D, Meurens F, Berri M, Chevaleyre C, Zanello G, Levast B, et al. New insights into the dual recruitment of IgA + B cells in the developing mammary gland. Mol Immunol. 2008;45(12):3354–62.

    Article  CAS  PubMed  Google Scholar 

  28. Weisz-Carrington P, Roux ME, Lamm ME. Plasma cells and epithelial immunoglobulins in the mouse mammary gland during pregnancy and lactation. J Immunol. 1977;119(4):1306–7.

    CAS  PubMed  Google Scholar 

  29. O’Brien J, Lyons T, Monks J, Lucia MS, Wilson RS, Hines L, et al. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol. 2010;176(3):1241–55.

    Article  PubMed  Google Scholar 

  30. O’Brien J, Schedin P. Macrophages in breast cancer: do involution macrophages account for the poor prognosis of pregnancy-associated breast cancer? J Mammary Gland Biol Neoplasia. 2009;14(2):145–57.

    Article  PubMed  Google Scholar 

  31. Harkonen PL, Vaananen HK. Monocyte-macrophage system as a target for estrogen and selective estrogen receptor modulators. Ann N Y Acad Sci. 2006;1089:218–27.

    Article  PubMed  Google Scholar 

  32. Routley CE, Ashcroft GS. Effect of estrogen and progesterone on macrophage activation during wound healing. Wound Repair Regen. 2009;17(1):42–50.

    Article  PubMed  Google Scholar 

  33. De M, Wood GW. Influence of oestrogen and progesterone on macrophage distribution in the mouse uterus. J Endocrinol. 1990;126(3):417–24.

    Article  CAS  PubMed  Google Scholar 

  34. Russell JS, McGee SO, Ip MM, Kuhlmann D, Masso-Welch PA. Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland stromal remodeling. J Nutr. 2007;137(5):1200–7.

    CAS  PubMed  Google Scholar 

  35. Masso-Welch PA, Zangani D, Ip C, Vaughan MM, Shoemaker S, Ramirez RA, et al. Inhibition of angiogenesis by the cancer chemopreventive agent conjugated linoleic acid. Cancer Res. 2002;62(15):4383–9.

    CAS  PubMed  Google Scholar 

  36. Gouon-Evans V, Lin EY, Pollard JW. Requirement of macrophages and eosinophils and their cytokines/chemokines for mammary gland development. Breast Cancer Res. 2002;4(4):155–64.

    Article  PubMed  Google Scholar 

  37. Pixley FJ, Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol. 2004;14(11):628–38.

    Article  CAS  PubMed  Google Scholar 

  38. Lin EY, Gouon-Evans V, Nguyen AV, Pollard JW. The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia. 2002;7(2):147–62.

    Article  PubMed  Google Scholar 

  39. Ingman WV, Wyckoff J, Gouon-Evans V, Condeelis J, Pollard JW. Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland. Dev Dyn. 2006;235(12):3222–9.

    Article  CAS  PubMed  Google Scholar 

  40. Gyorki DE, Asselin-Labat ML, van Rooijen N, Lindeman GJ, Visvader JE. Resident macrophages influence stem cell activity in the mammary gland. Breast Cancer Res. 2009;11(4):R62.

    Article  PubMed  Google Scholar 

  41. Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P. Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med. 1997;185(4):785–90.

    Article  CAS  PubMed  Google Scholar 

  42. Colbert DC, McGarry MP, O'Neill K, Lee NA, Lee JJ. Decreased size and survival of weanling mice in litters of IL-5-/ -mice are a consequence of the IL-5 deficiency in nursing dams. Contemp Top Lab Anim Sci. 2005;44(3):53–5.

    CAS  PubMed  Google Scholar 

  43. Dent LA, Strath M, Mellor AL, Sanderson CJ. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990;172(5):1425–31.

    Article  CAS  PubMed  Google Scholar 

  44. Daniel CW, Robinson S, Silberstein GB. The transforming growth factors beta in development and functional differentiation of the mouse mammary gland. Adv Exp Med Biol. 2001;501:61–70.

    CAS  PubMed  Google Scholar 

  45. Wilson E, Butcher EC. CCL28 controls immunoglobulin (Ig)A plasma cell accumulation in the lactating mammary gland and IgA antibody transfer to the neonate. J Exp Med. 2004;200(6):805–9.

    Article  CAS  PubMed  Google Scholar 

  46. Watson CJ. Immune cell regulators in mouse mammary development and involution. J Anim Sci. 2009;87(13 Suppl):35–42.

    CAS  PubMed  Google Scholar 

  47. Khaled WT, Read EK, Nicholson SE, Baxter FO, Brennan AJ, Came PJ, et al. The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development. Development. 2007;134(15):2739–50.

    Article  CAS  PubMed  Google Scholar 

  48. Baratta M, Motta M, Accornero P. Leptin reduces the inhibitory effect of IL-1 beta on beta-casein gene expression in differentiated mammary cells. Vet Res Commun. 2005;29 Suppl 2:153–5.

    Article  PubMed  Google Scholar 

  49. Clarkson RW, Wayland MT, Lee J, Freeman T, Watson CJ. Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression. Breast Cancer Res. 2004;6(2):R92–109.

    Article  CAS  PubMed  Google Scholar 

  50. Kaplan MH, Schindler U, Smiley ST, Grusby MJ. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 1996;4(3):313–9.

    Article  CAS  PubMed  Google Scholar 

  51. Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol. 2008;1(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  52. Low EN, Zagieboylo L, Martino B, Wilson E. IgA ASC accumulation to the lactating mammary gland is dependent on VCAM-1 and alpha4 integrins. Mol Immunol. 2010;47(7–8):1608–12.

    Article  CAS  PubMed  Google Scholar 

  53. Strange R, Li F, Saurer S, Burkhardt A, Friis RR. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development. 1992;115(1):49–58.

    CAS  PubMed  Google Scholar 

  54. Stein T, Morris JS, Davies CR, Weber-Hall SJ, Duffy MA, Heath VJ, et al. Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res. 2004;6(2):R75–91.

    Article  CAS  PubMed  Google Scholar 

  55. Lilla JN, Joshi RV, Craik CS, Werb Z. Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem. 2009;284(20):13792–803.

    Article  CAS  PubMed  Google Scholar 

  56. Lund LR, Bjorn SF, Sternlicht MD, Nielsen BS, Solberg H, Usher PA, et al. Lactational competence and involution of the mouse mammary gland require plasminogen. Development. 2000;127(20):4481–92.

    CAS  PubMed  Google Scholar 

  57. Monks J, Smith-Steinhart C, Kruk ER, Fadok VA, Henson PM. Epithelial cells remove apoptotic epithelial cells during post-lactation involution of the mouse mammary gland. Biol Reprod. 2008;78(4):586–94.

    Article  CAS  PubMed  Google Scholar 

  58. Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, et al. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med. 2006;12(3):317–23.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Jodi Goldberg for critical reading of this manuscript. JRR is supported by a pre-doctoral fellowship on the T32 CA009138 Cancer Biology Training Grant.

Author information

Authors and Affiliations

  1. Department of Lab Medicine and Pathology, Graduate Program in Microbiology, Immunology and Cancer Biology, Masonic Cancer Center, University of Minnesota, 420 Delaware St. SE, MMC 609, Minneapolis, MN, 55455, USA

    Johanna R. Reed & Kathryn L. Schwertfeger

Authors
  1. Johanna R. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn L. Schwertfeger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathryn L. Schwertfeger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reed, J.R., Schwertfeger, K.L. Immune Cell Location and Function During Post-Natal Mammary Gland Development. J Mammary Gland Biol Neoplasia 15, 329–339 (2010). https://doi.org/10.1007/s10911-010-9188-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-010-9188-7

Keywords

Search

Navigation