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 6

Increased beiging and eosinophils in the scWAT of Ifnγ–/– mice.

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Increased beiging and eosinophils in the scWAT of Ifnγ–/– mice. (A) Repr...
(A) Representative images of UCP1 IF staining in the scWAT of WT or Rag1–/– mice treated with PBS or adoptively transferred with 5 × 106 WT-derived or Ifnγ–/–-derived CD8+ T cells, once a week for 2 weeks. Scale bar: 100 μm. (B) The relative UCP1 mean intensity in the above groups. Values represent mean ± SD intensity of 15 patches for every image. n = 3 per group. ***P < 0.001, 2-way ANOVA. (C) Representative images of H&E and UCP1 IF staining of scWAT from WT and Ifnγ–/– mice. Scale bar: 100 μm. n = 3 per group. Data shown are derived from 1 experiment. (D) Gating strategy for the identification of eosinophils gated on viable CD45+DAPI– cells and further identified as CD11b+Siglec F+ cells. Data shown are depicted as percentages. Flow cytometry was performed after pooling n ≥ 4 mice per group. (E) Gating strategy for the identification of total ILCs in WT mice or Rag1–/– mice treated with PBS or adoptively transferred with 5 × 106 WT CD8+ T cells or CD8+ T cells derived from Ifnγ–/– mice, once a week for 2 weeks. Percentages of cells positive for CD90.2+Sca-1+Lin– gated on the viable CD45+DAPI– cells are depicted on the flow cytometry plots. Flow cytometry was performed after pooling n ≥ 4 mice per group. (F) Absolute numbers of total ILCs (CD90.2+ Sca-1+Lin–) per gram of tissue in scWAT of WT and Ifnγ–/– mice. n = 5 per group. Data are presented as mean ± SEM. *P < 0.05, Student’s t test.