CD8+ T cells in beige adipogenesis and energy homeostasis
Maria Moysidou, Sevasti Karaliota, Elisavet Kodela, Maria Salagianni, Yassemi Koutmani, Antonia Katsouda, Konstantia Kodella, Panagiotis Tsakanikas, Styliani Ourailidou, Evangelos Andreakos, Nikolaos Kostomitsopoulos, Dimitris Skokos, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Stefan Bornstein, Mark W. Sleeman, Triantafyllos Chavakis, Katia P. Karalis
Maria Moysidou, Sevasti Karaliota, Elisavet Kodela, Maria Salagianni, Yassemi Koutmani, Antonia Katsouda, Konstantia Kodella, Panagiotis Tsakanikas, Styliani Ourailidou, Evangelos Andreakos, Nikolaos Kostomitsopoulos, Dimitris Skokos, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Stefan Bornstein, Mark W. Sleeman, Triantafyllos Chavakis, Katia P. Karalis
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Research Article Metabolism

CD8+ T cells in beige adipogenesis and energy homeostasis

Abstract

Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1–/– mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8+ T cell deficiency accounts for the enhanced beige adipogenesis in Rag1–/– mice. Consistently, we identified that CD8–/– mice also presented with enhanced beige adipogenesis. The inhibitory effect of CD8+ T cells on beige adipogenesis was reversed by blockade of IFN-γ. All together, our findings identify an effect of CD8+ T cells in regulating energy dissipation in lean WAT, mediated by IFN-γ modulation of the abundance of resident immune cells and of local catecholaminergic activity. Our results provide a plausible explanation for the clinical signs of metabolic dysfunction in diseases characterized by altered CD8+ T cell abundance and suggest targeting of CD8+ T cells as a promising therapeutic approach for obesity and other diseases with altered energy homeostasis.

Authors

Maria Moysidou, Sevasti Karaliota, Elisavet Kodela, Maria Salagianni, Yassemi Koutmani, Antonia Katsouda, Konstantia Kodella, Panagiotis Tsakanikas, Styliani Ourailidou, Evangelos Andreakos, Nikolaos Kostomitsopoulos, Dimitris Skokos, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Stefan Bornstein, Mark W. Sleeman, Triantafyllos Chavakis, Katia P. Karalis

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Figure 4

Adoptive transfer of CD8+ T cells inhibits increased scWAT beiging in Rag1–/– mice exposed to cold environment.

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Adoptive transfer of CD8+ T cells inhibits increased scWAT beiging in Ra...
Data shown are from the scWAT of WT, Rag1–/–, or Rag1–/– mice reconstituted with 5 × 106 CD8+ T cells, once a week for 2 weeks. (A) Core temperature measurements. n ≥ 4 per group. (B) Representative images of H&E and IF staining of UCP1 and TH. Arrows represent the TH+ cells. Scale bar: 100 μm. n ≥ 3 per group. (C) Relative expression of thermogenic, lipid metabolism, and adrenergic receptors genes in the scWAT of age-matched mice, housed at 4°C for 2 days at the end of the second week. Data are shown as mean expression normalized to actin ± SEM. n ≥ 5 per group. Data shown are derived from one representative of 2 independent experiments. (D) Representative percentages of eosinophils (CD11b+Siglec F+), housed at 4oC for 2 days. Data shown are representative of 2 independent experiments. Flow cytometry was performed after pooling n ≥ 4 mice per group. (E) Results are expressed as percentages of CD11b+Siglec F+ eosinophils, gated on the viable CD45+DAPI– cells. n ≥ 4 per group. (F) Representative percentages of ILCs positive for CD90.2+ Sca-1+ Lin– in WT mice or Rag1–/– mice treated with PBS or adoptively transferred with CD8+ T cells (5 × 106), once a week for 2 weeks, and housed at 4°C for 2 days are depicted on the flow cytometry plots. Data shown are representative of 2 independent experiments. Flow cytometry was performed after pooling n ≥ 4 mice per group. (G) Results are expressed as percentages of CD90.2+Sca-1+ Lin– gated on the viable CD45+DAPI– cells. n ≥ 4 per group. Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, 1-way ANOVA with Bonferroni’s post test.