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The pancreas anatomy conditions the origin and properties of resident macrophages

Calderon, Boris, Carrero, Javier A., Ferris, Stephen T., Sojka, Dorothy K., Moore, Lindsay, Epelman, Slava, Murphy, Kenneth M., Yokoyama, Wayne M. +2 more·2015·Journal of Experimental Medicine

Abstract

We examine the features, origin, turnover, and gene expression of pancreatic macrophages under steady state. The data distinguish macrophages within distinct intrapancreatic microenvironments and suggest how macrophage phenotype is imprinted by the local milieu. Macrophages in islets of Langerhans and in the interacinar stroma are distinct in origin and phenotypic properties. In islets, macrophages are the only myeloid cells: they derive from definitive hematopoiesis, exchange to a minimum with blood cells, have a low level of self-replication, and depend on CSF-1. They express Il1b and Tnfa transcripts, indicating classical activation, M1, under steady state. The interacinar stroma contains two macrophage subsets. One is derived from primitive hematopoiesis, with no interchange by blood cells and alternative, M2, activation profile, whereas the second is derived from definitive hematopoiesis and exchanges with circulating myeloid cells but also shows an alternative activation profile. Complete replacement of islet and stromal macrophages by donor stem cells occurred after lethal irradiation with identical profiles as observed under steady state. The extraordinary plasticity of macrophages within the pancreatic organ and the distinct features imprinted by their anatomical localization sets the base for examining these cells in pathological conditions.

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  • Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, unlike most other tissue-resident macrophages.

    “Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, in contrast to most other tissue-resident macrophages (which also initially originate from yolk sac-derived macrophages, but are partially or fully replaced by fetal liver- or blood monocyte-derived macrophages [Bain et al., 2014, Calderon et”

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Authors
Calderon, B., Carrero, J. A., Ferris, S. T., Sojka, D. K., Moore, L., Epelman, S., Murphy, K. M., Yokoyama, W. M., Randolph, G. J., & Unanue, E. R.
Affiliations
Department of Pathology and Immunology 1 ; 2 and 3 ; and 4
Venue
Journal of Experimental Medicine
Published
2015-09-07
Volume
212
Issue
10
Pages
1497-1512
ISSN
  • 1540-9538
  • 0022-1007
Cited by
308
References
13
Language
en

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