Resident T cells orchestrate adipose tissue remodeling in a site peripheral to infection

Kabat, A. M.; Hackl, A.; Sanin, D. E.; Zeis, P.; Grzes, K. M.; Baixauli, F.; Kyle, R.; Caputa, G.; Edwards-Hicks, J.; Villa, M.; Rana, N.; Curtis, J. D.; Castoldi, A.; Cupovic, J.; Dreesen, L.; Sibilia, M.; Pospisilik, J. A.; Urban, J. F.; Grün, D.; Pearce, E. L.; Pearce, E. J.

doi:10.1101/2022.02.24.481701

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bioRxiv · 10.1101/2022.02.24.481701

Resident T cells orchestrate adipose tissue remodeling in a site peripheral to infection

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Abstract

Infection with helminth parasites can affect adiposity, but underlying mechanisms that regulate this process are unclear. We found that fat content of mesenteric adipose tissue (mAT) declined in mice during infection with gut-restricted parasitic worms. This was associated with the accumulation of metabolically activated, immunostimulatory cytokine- and extracellular matrix-secreting multipotent stromal cells, which had potential to differentiate into preadipocytes. Concomitantly, mAT became infiltrated with Th2 lymphocytes that took up long-term residence and responded to signals from stromal cells by producing stromal cell-stimulating cytokines, including Amphiregulin. Signals delivered by Amphiregulin to stromal cells were required for immunity to infection. Our findings reveal intricate intercellular communication between Th2 cells and adipocyte progenitors and link immunity to intestinal infection to T cell-dependent effects on the adipocyte lineage.

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Kabat, A. M., Hackl, A., Sanin, D. E., Zeis, P., Grzes, K. M., Baixauli, F., Kyle, R., Caputa, G., Edwards-Hicks, J., Villa, M., Rana, N., Curtis, J. D., Castoldi, A., Cupovic, J., Dreesen, L., Sibilia, M., Pospisilik, J. A., Urban, J. F., Grün, D., Pearce, E. L., Pearce, E. J.. 2022-02-26. Resident T cells orchestrate adipose tissue remodeling in a site peripheral to infection. https://doi.org/10.1101/2022.02.24.481701

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