Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and co-localize in fibroblast niches
Fibroblasts are dynamic structural cells that direct both beneficial tissue repair and pathologic organ fibrosis through interactions with tissue-resident type 2 and type 3/17 lymphocytes (T2L and T3L). We performed spatial transcriptomics to profile heterogenous fibroblast populations within fibrotic, adventitial, and parenchymal regions of resting and fibrotic murine livers as well as to determine their crosstalk with T2L and T3L. Our analysis suggests a spatially associated crosstalk between liver lymphocytes and fibroblast niches. Overall design: Four mouse models with genetic depletion of IL-5+ lymphocytes and IL-17A+ lymphocytes were used for the analysis: 4-week CCl4- and placebo-treated IL5-Cre mice, 4-week CCl4-treated IL-5 deleter mice, and 4-week CCl4-treated IL-5;IL-17A double deleter mice.