Journal Article

DKFZ-2026-01684

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png ILC2s regulate a fibroblast progenitor niche in the pancreas.

Yip, T. ; Stockis, J. ; Simpson, C. ; McCartney, E. E. ; Raghunathan, S. ; Rangel-Sosa, M. M. ; Hummel, S. N. ; Moreno-Vicente, J. ; Raddi, G. ; Garcia, C. ; Linkute, R. ; Pinaud, S. ; Cheng, M. F. ; Hill, L. A. ; Underhill, T. M. ; Rodewald, H.-R.DKFZ* ; Schneider, C. ; Jørgensen, C. ; McKenzie, A. N. J. ; Acton, S. E. ; Seale, P. ; Clatworthy, M. R. ; Buechler, M. B. ; Halim, T. Y. F.

2026
American Association for the Advancement of Science Washington, DC

Abstract: Local fibroblast development and densities influence organ health and disease, although it remains unclear how tissue fibroblast topography is controlled in situ. Here, we defined Group 2 innate lymphoid cells (ILC2s) as key regulators of fibroblast homeostasis in the pancreas. ILC2s colocalized with fibroblasts expressing the genes Pi16+Dpp4+Ly6c+ in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2s specifically regulated the expansion of Pi16+Dpp4+Ly6c+ fibroblasts, which have progenitor capacity, while restraining differentiated intraparenchymal Col15a1+ fibroblasts during inflammation. These circuits reinforced fibroblast numbers after injury and set an inflammatory threshold. The ILC2 and Pi16+Dpp4+Ly6c+ fibroblast progenitor niche expanded around tumors and controlled cancer-associated fibroblast ontogeny and density. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Cell Differentiation (MeSH) ; Fibroblasts: physiology (MeSH) ; Fibroblasts: cytology (MeSH) ; Fibroblasts: immunology (MeSH) ; Homeostasis (MeSH) ; Immunity, Innate (MeSH) ; Lymphocytes: immunology (MeSH) ; Lymphocytes: physiology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Pancreas, Exocrine: cytology (MeSH) ; Pancreas, Exocrine: immunology (MeSH) ; Pancreatic Neoplasms: immunology (MeSH) ; Pancreatic Neoplasms: pathology (MeSH) ; Stem Cell Niche: immunology (MeSH) ; Stem Cells (MeSH) ; Pancreatitis: immunology (MeSH) ; Pancreatitis: pathology (MeSH) ; Collagen: genetics (MeSH) ; Collagen: metabolism (MeSH) ; Male (MeSH) ; collagen XV, mouse ; Collagen

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Contributing Institute(s):

1. Zelluläre Immunologie (D110)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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