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Brown adipose tissue harbors a distinct sub-population of regulatory T cells.

Medrikova D, Sijmonsma TP, Sowodniok K, Richards DM, Delacher M, Sticht C, Gretz N, Schafmeier T, Feuerer M, Herzig S - PLoS ONE (2015)

Bottom Line: Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control.Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature.As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

View Article: PubMed Central - PubMed

Affiliation: Joint Research Division Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, 69120, Heidelberg, Germany.

ABSTRACT
Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

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Inflammatory status of adipose tissue.Real-time RT-PCR analysis of (A) brown adipose tissue (BAT) and (B) subcutaneous white adipose tissue of Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice after cold exposure. Ucp1, uncoupling protein 1; Cidea,cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; Dio2,deiodinase, iodothyronine, type II; Pparg, peroxisome proliferator-activated receptor gamma; Prdm16, PR domain containing 16; Cd68, Cd68 antigen; Ccl2,chemokine (C-C motif) ligand 2; Tnfa, tumor necrosis factor alpha; Ifng, interferon, gamma; Mrc1, mannose receptor, C type 1; Mgl1, macrophage galactose-type C-type lectin 1; Arg1,arginase 1; Il-10, interleukin 10; Il-4, interleukin 4. Data are mean ± SD (n = 9–10); *p<0.05 (Student’s t-test). (C) Representative hematoxylin and eosin (H&E) staining (left) and immunohistochemical anti-MAC-2 staining (right; brown color) in BAT from PBS and DT mice. Scale bar 100 μm. Quantification of MAC-2 positive area (panel below MAC-2 staining) as a percentage of total area.
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pone.0118534.g004: Inflammatory status of adipose tissue.Real-time RT-PCR analysis of (A) brown adipose tissue (BAT) and (B) subcutaneous white adipose tissue of Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice after cold exposure. Ucp1, uncoupling protein 1; Cidea,cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; Dio2,deiodinase, iodothyronine, type II; Pparg, peroxisome proliferator-activated receptor gamma; Prdm16, PR domain containing 16; Cd68, Cd68 antigen; Ccl2,chemokine (C-C motif) ligand 2; Tnfa, tumor necrosis factor alpha; Ifng, interferon, gamma; Mrc1, mannose receptor, C type 1; Mgl1, macrophage galactose-type C-type lectin 1; Arg1,arginase 1; Il-10, interleukin 10; Il-4, interleukin 4. Data are mean ± SD (n = 9–10); *p<0.05 (Student’s t-test). (C) Representative hematoxylin and eosin (H&E) staining (left) and immunohistochemical anti-MAC-2 staining (right; brown color) in BAT from PBS and DT mice. Scale bar 100 μm. Quantification of MAC-2 positive area (panel below MAC-2 staining) as a percentage of total area.

Mentions: These data supported the hypothesis that Treg cells may exert regulatory functions in BAT activation in response to cold stimulation. Consistent with impaired BAT activity, heat production per animal was decreased (S1 Fig.). Also, selective gene expression profiling revealed that particularly genes in the thermogenic gene program were downregulated in cold-exposed BAT upon Treg cell deficiency (Fig. 4A), without affecting browning markers in subcutaneous WAT (Fig. 4B). Pro-inflammatory markers, including chemokine (C-C motif) ligand 2 (Ccl2) and tumor necrosis factor alpha (Tnfa), were found to be induced upon the lack of Treg cell function. Along with these observations, Treg-deficient BAT displayed a substantial increase in macrophage infiltration (Fig. 4C).


Brown adipose tissue harbors a distinct sub-population of regulatory T cells.

Medrikova D, Sijmonsma TP, Sowodniok K, Richards DM, Delacher M, Sticht C, Gretz N, Schafmeier T, Feuerer M, Herzig S - PLoS ONE (2015)

Inflammatory status of adipose tissue.Real-time RT-PCR analysis of (A) brown adipose tissue (BAT) and (B) subcutaneous white adipose tissue of Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice after cold exposure. Ucp1, uncoupling protein 1; Cidea,cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; Dio2,deiodinase, iodothyronine, type II; Pparg, peroxisome proliferator-activated receptor gamma; Prdm16, PR domain containing 16; Cd68, Cd68 antigen; Ccl2,chemokine (C-C motif) ligand 2; Tnfa, tumor necrosis factor alpha; Ifng, interferon, gamma; Mrc1, mannose receptor, C type 1; Mgl1, macrophage galactose-type C-type lectin 1; Arg1,arginase 1; Il-10, interleukin 10; Il-4, interleukin 4. Data are mean ± SD (n = 9–10); *p<0.05 (Student’s t-test). (C) Representative hematoxylin and eosin (H&E) staining (left) and immunohistochemical anti-MAC-2 staining (right; brown color) in BAT from PBS and DT mice. Scale bar 100 μm. Quantification of MAC-2 positive area (panel below MAC-2 staining) as a percentage of total area.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340926&req=5

pone.0118534.g004: Inflammatory status of adipose tissue.Real-time RT-PCR analysis of (A) brown adipose tissue (BAT) and (B) subcutaneous white adipose tissue of Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice after cold exposure. Ucp1, uncoupling protein 1; Cidea,cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; Dio2,deiodinase, iodothyronine, type II; Pparg, peroxisome proliferator-activated receptor gamma; Prdm16, PR domain containing 16; Cd68, Cd68 antigen; Ccl2,chemokine (C-C motif) ligand 2; Tnfa, tumor necrosis factor alpha; Ifng, interferon, gamma; Mrc1, mannose receptor, C type 1; Mgl1, macrophage galactose-type C-type lectin 1; Arg1,arginase 1; Il-10, interleukin 10; Il-4, interleukin 4. Data are mean ± SD (n = 9–10); *p<0.05 (Student’s t-test). (C) Representative hematoxylin and eosin (H&E) staining (left) and immunohistochemical anti-MAC-2 staining (right; brown color) in BAT from PBS and DT mice. Scale bar 100 μm. Quantification of MAC-2 positive area (panel below MAC-2 staining) as a percentage of total area.
Mentions: These data supported the hypothesis that Treg cells may exert regulatory functions in BAT activation in response to cold stimulation. Consistent with impaired BAT activity, heat production per animal was decreased (S1 Fig.). Also, selective gene expression profiling revealed that particularly genes in the thermogenic gene program were downregulated in cold-exposed BAT upon Treg cell deficiency (Fig. 4A), without affecting browning markers in subcutaneous WAT (Fig. 4B). Pro-inflammatory markers, including chemokine (C-C motif) ligand 2 (Ccl2) and tumor necrosis factor alpha (Tnfa), were found to be induced upon the lack of Treg cell function. Along with these observations, Treg-deficient BAT displayed a substantial increase in macrophage infiltration (Fig. 4C).

Bottom Line: Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control.Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature.As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

View Article: PubMed Central - PubMed

Affiliation: Joint Research Division Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, 69120, Heidelberg, Germany.

ABSTRACT
Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

Show MeSH
Related in: MedlinePlus