A Stromal Cell Niche Sustains ILC2-Mediated Type-2 Conditioning in Adipose Tissue

Group-2 innate lymphoid cells (ILC2), type-2 cytokines and eosinophils, have all been implicated in sustaining adipose tissue homeostasis. However, the interplay between the stroma and adipose-resident immune cells is less well understood. We identify that white adipose tissue-resident multipotent stromal cells (WAT-MSCs) can act as a reservoir for IL-33, especially after cell stress, but also provide additional signals for sustaining ILC2. Indeed, we demonstrate that WAT-MSCs also support ICAM-1-mediated proliferation and activation of LFA-1-expressing ILC2s. Consequently, ILC2-derived IL-4 and IL-13 feed-back to induce eotaxin secretion from WAT-MSCs supporting eosinophil recruitment. Thus, MSCs provide a niche for multifaceted dialogue with ILC2 to sustain a type-2 immune environment in WAT. White adipose tissue from IL-33-critine heterozygous reporter mice was mechanically dissociated in RPMI-1640, and digested with collagenase I (Life Technologies), DNase I (Roche) at 37oC whilst shaking. Lin-CD45-Epcam-CD31-CD24-PDGFRα+CD34+Sca1+Podoplanin+ IL-33-citrine+ or IL-33-citrine- WAT-MSCs, Lin-CD45-Epcam+ and Lin-CD45-Epcam-CD31+ were sorted by flow cytometry using Sony iCyt Synergy (Sony) to >95% purity. Three replicates from independent experiments were obtained and sequenced for RNA-seq.