Resident TH2 cells orchestrate adipose tissue remodeling at a site adjacent to 
infection

Kabat, Agnieszka M; Hackl, Alexandra; Sanin, David E; Zeis, Patrice; Grzes, Katarzyna M; Baixauli, Francesc; Kyle, Ryan; Caputa, George; Edwards-Hicks, Joy; Villa, Matteo; Rana, Nisha; Curtis, Jonathan D; Castoldi, Angela; Cupovic, Jovana; Dreesen, Leentje; Sibilia, Maria; Pospisilik, J Andrew; Urban Jr, Joseph F; Grün, Dominic; Pearce, Erika Laine; Pearce, Edward Jonathen

doi:10.1126/sciimmunol.add3263

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Resident T_H2 cells orchestrate adipose tissue remodeling at a site adjacent to infection

MPS-Authors

Kabat, Agnieszka M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hackl, Alexandra
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sanin, David E
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Zeis, Patrice
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Grzes, Katarzyna M
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Baixauli, Francesc
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kyle, Ryan
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Caputa, George
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks, Joy
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Villa, Matteo
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rana, Nisha
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis, Jonathan D
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Castoldi, Angela
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cupovic, Jovana
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Grün, Dominic
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201431

Pearce, Erika Laine
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce, Edward Jonathen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Kabat, A. M., Hackl, A., Sanin, D. E., Zeis, P., Grzes, K. M., Baixauli, F., et al. (2022). Resident T_H2 cells orchestrate adipose tissue remodeling at a site adjacent to infection. Science Immunology, 7: eadd3263. doi:10.1126/sciimmunol.add3263.

Cite as: https://hdl.handle.net/21.11116/0000-000D-1316-5

Abstract

Type 2 immunity is associated with adipose tissue (AT) homeostasis and infection with parasitic helminths, but whether AT participates in immunity to these parasites is unknown. We found that the fat content of mesenteric AT (mAT) declined in mice during infection with a gut-restricted helminth. This was associated with the accumulation of metabolically activated, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and extracellular matrix (ECM)-producing stromal cells. These cells shared transcriptional features, including the expression of Dpp4 and Pi16, with multipotent progenitor cells (MPC) that have been identified in numerous tissues and are reported to be capable of differentiating into fibroblasts and adipocytes. Concomitantly, mAT became infiltrated with resident T helper 2 (T_H2) cells that responded to TSLP and IL-33 by producing stromal cell-stimulating cytokines, including transforming growth factor β1 (TGFβ₁) and amphiregulin. These T_H2 cells expressed genes previously associated with type 2 innate lymphoid cells (ILC2), including Nmur1, Calca, Klrg1, and Arg1, and persisted in mAT for at least 11 months after anthelmintic drug-mediated clearance of infection. We found that MPC and T_H2 cells localized to ECM-rich interstitial spaces that appeared shared between mesenteric lymph node, mAT, and intestine. Stromal cell expression of epidermal growth factor receptor (EGFR), the receptor for amphiregulin, was required for immunity to infection. Our findings point to the importance of MPC and T_H2 cell interactions within the interstitium in orchestrating AT remodeling and immunity to an intestinal infection.