Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchi / immunology
  • Cytokines / immunology
  • Immunity, Innate / immunology*
  • Interleukin-13 / immunology
  • Interleukin-33 / immunology
  • Lymphocytes / immunology*
  • Mice
  • Stromal Cells / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / immunology
  • Thymic Stromal Lymphopoietin


  • Cytokines
  • Interleukin-13
  • Interleukin-33
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse