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
Affiliations
Henna Lehtonen
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
Heli Jokela
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
Julian Hofmann
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
Lauriina Tola
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
Arfa Mehmood
Institute of Biomedicine, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Florent Ginhoux
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
Burkhard Becher
Institute of Experimental Immunology, University of Zürich, 8057 Zurich, Switzerland
Melanie Greter
Institute of Experimental Immunology, University of Zürich, 8057 Zurich, Switzerland
Gennady G. Yegutkin
InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; MediCity Research Laboratory, University of Turku, 20520 Turku, Finland
Marko Salmi
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
Heidi Gerke
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
Pia Rantakari
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; Corresponding author
Summary: 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.
