ARI MOLOFSKY LAB @ UCSF

Tissue Niches of Type 2 Lymphocytes

One area of laboratory focus is to understand the tissue niches which support and regulate type 2 lymphocytes, including group 2 innate lymphoid cells (ILC2), Th2 tissue-resident memory cells, and type 2-skewed Tregs. Using a combination of advanced imaging, genetics, and molecular approaches, we have identified specific micro-anatomic sites where these type 2 lymphocytes reside and are working to characterize these sites of immune-tissue cross-talk.

We recently published work defining a conserved microanatomical tissue niche of ILC2s. In multiple tissues, ILC2s predominantly localize to adventitial cuffs, the outermost layer of larger blood vessels and other tubular structures, like airways. Adventitial cuffs are dynamic spaces enriched with extracellular matrix components, small blood vessels, lymphatics, nerves, and immune cells. Within this microanatomical site, ILC2s are intimately associated with adventitial fibroblasts (AFs), a population of mesenchymal stromal cells (MSCs). Lung AFs produce interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) and are key local regulators of ILC2s and type 2 immunity. Reciprocally, ILC2s support AF expansion and IL-33 expression. We hope that continued study of these dynamic sites will lead to a better understanding of type 2 lymphocyte interaction with ASCs and other immune cell populations within their discrete microanatomical niche and how adventitial immune responses are regulated to impact the physiology of their host tissue.