Animals; Female; Immunity, Mucosal/immunology; Macrophages/immunology; Macrophages/metabolism; Mammary Glands, Animal/growth & development; Mammary Glands, Animal/immunology; Sheep, Domestic/growth & development; Sheep, Domestic/immunology; Stromal Cells/immunology; Stromal Cells/metabolism; Immunity, Mucosal; Macrophages; Mammary Glands, Animal; Sheep, Domestic; Stromal Cells; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); General Agricultural and Biological Sciences; General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] The human breast and ovine mammary gland undergo striking levels of postnatal development, leading to formation of terminal duct lobular units (TDLUs). Here we interrogate aspects of sheep TDLU growth as a model of breast development and to increase understanding of ovine mammogenesis. The distributions of epithelial nuclear Ki67 positivity differ significantly between younger and older lambs. Ki67 expression is polarised to the leading edge of the developing TDLUs. Intraepithelial ductal macrophages exhibit periodicity and considerably increased density in lambs approaching puberty. Stromal macrophages are more abundant centrally than peripherally. Intraepithelial T lymphocytes are more numerous in older lambs. Stromal hotspots of Ki67 expression colocalize with immune cell aggregates that exhibit distinct organisation consistent with tertiary lymphoid structures. The lamb mammary gland thus exhibits a dynamic mucosal and stromal immune microenvironment and constitutes a valuable model system that provides new insights into postnatal breast development.
Disciplines :
Veterinary medicine & animal health Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Nagy, Dorottya ; Université de Liège - ULiège ; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
Gillis, Clare M C; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
Davies, Katie; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK
Fowden, Abigail L; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK
Rees, Paul; College of Engineering, Swansea University, Fabian Way, Crymlyn Burrows, Swansea, UK ; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Wills, John W ; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK. jw2020@cam.ac.uk
Hughes, Katherine ; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK. kh387@cam.ac.uk
Language :
English
Title :
Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment.
This work was supported by a grant from the British Veterinary Association Animal Welfare Foundation Norman Hayward Fund awarded to KH [grant number NHF_2016_03_KH]. JWW is grateful to Girton College and the University of Cambridge Herchel-Smith Fund for supporting him with Fellowships. The authors would like to acknowledge the UK Engineering and Physical Sciences Research Council (grant EP/ N013506/1), and the UK Biotechnology and Biological Sciences Research Council (grant number BB/P026818/1), both awarded to PR, for supporting the work. The authors gratefully acknowledge the excellent technical expertise of Debbie Sabin in the preparation of histology sections and unstained tissue sections. Some confocal microscopy images were acquired using equipment at the Cambridge Advanced Imaging Centre (CAIC) and the authors thank members of the CAIC for their advice and support. The Ethics and Welfare Committee of the Department of Veterinary Medicine, University of Cambridge, reviewed the study plan relating to the use of ruminant tissue collected following post mortem examination for the study of mammary gland biology (reference: CR223) and the work of this committee is gratefully recognised. The data detailed in this manuscript were presented in part at the 2020 Winter Meeting of the Pathological Society of Great Britain & Ireland (presentation: 21 January 2020), the 2020 American College of Veterinary Pathologists Annual Meeting (presentation: 30 October 2020), and the 2021 Anatomical Society Virtual Winter Meeting (presentation: 7 January 2021).
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