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Immunity. 2019 Mar 19;50(3):707-722.e6. doi: 10.1016/j.immuni.2019.02.002. Epub 2019 Feb 26.

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Author information

1
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
3
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: ari.molofsky@ucsf.edu.

Abstract

Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.

KEYWORDS:

3D-imaging; IL-33; ILC2s; TSLP; Th2 cells; allergic asthma; group 2 innate lymphoid cells; mesenchymal cells; resident lymphocytes; stromal cells; tissue niches; type 2 immunity

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