Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance

Henna Lehtonen; Heli Jokela; Julian Hofmann; Lauriina Tola; Arfa Mehmood; Florent Ginhoux; Burkhard Becher; Melanie Greter; Gennady G Yegutkin; Marko Salmi; Heidi Gerke; Pia Rantakari

doi:10.1016/j.celrep.2024.115227

Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance

Cell Rep. 2025 Jan 21;44(2):115227. doi: 10.1016/j.celrep.2024.115227. Online ahead of print.

Authors

Affiliations

¹ Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland.
² Institute of Biomedicine, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland.
³ Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif 94800, France; Translational Immunology Institute, SingHealth Duke-NUS, Singapore 169856, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁴ Institute of Experimental Immunology, University of Zürich, 8057 Zurich, Switzerland.
⁵ InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
⁶ Institute of Biomedicine, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
⁷ Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland. Electronic address: pia.rantakari@utu.fi.

PMID: 39841599
DOI: 10.1016/j.celrep.2024.115227

Abstract

The pituitary gland is the central endocrine regulatory organ producing and releasing hormones that coordinate major body functions. The physical location of the pituitary gland at the base of the brain, though outside the protective blood-brain barrier, leads to an unexplored special immune environment. Using single-cell transcriptomics, fate mapping, and imaging, we characterize pituitary-resident macrophages (pitMØs), revealing their heterogeneity and spatial specialization. Microglia-like macrophages (ml-MACs) are enriched in the posterior pituitary, while other pitMØs in the anterior pituitary exhibit close interactions with hormone-secreting cells. Importantly, all pitMØs originate from early yolk sac progenitors and maintain themselves through self-renewal, independent of bone marrow-derived monocytes. Macrophage depletion experiments unveil the role of macrophages in regulating intrapituitary hormonal balance through extracellular ATP-mediated intercellular signaling. Altogether, these findings provide information on pituitary gland macrophages and advance our understanding of immune-endocrine system crosstalk.

Keywords: CP: Immunology; hormonal balance; microglia-like cells; pituitary gland; tissue-resident macrophages; yolk sac origin.