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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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Treg cell depletion and metabolic phenotyping.(A) Real-time RT-PCR analysis of FoxP3 expression in brown adipose tissue (BAT) and spleen in Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice. (B) Oxygen consumption, (C) food intake and (D) locomotor activity during 4 consecutive days at 22°C and 4°C. Injections of vehicle (PBS) or diphtheria toxin (DT) were performed at day 2 and day 3. Values are mean ± SD (n = 9–10); *P<0.05 (Student’s t-test).
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pone.0118534.g002: Treg cell depletion and metabolic phenotyping.(A) Real-time RT-PCR analysis of FoxP3 expression in brown adipose tissue (BAT) and spleen in Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice. (B) Oxygen consumption, (C) food intake and (D) locomotor activity during 4 consecutive days at 22°C and 4°C. Injections of vehicle (PBS) or diphtheria toxin (DT) were performed at day 2 and day 3. Values are mean ± SD (n = 9–10); *P<0.05 (Student’s t-test).

Mentions: To next test the impact of Treg cells on systemic energy expenditure under cold conditions, we performed deep metabolic phenotyping of Treg-proficient and Treg-deficient mice. Due to the lack of fat-specific Treg targeting systems to date, we employed transgenic mice expressing the diphtheria toxin (DT) receptor under the control of Foxp3 gene regulatory elements [19]. Given the development of systemic immune dysfunction two weeks after DT administration in these animals [19], we restricted our analysis to the adaptation of systemic metabolism to an acute cold challenge and analyzed 48 h after Treg depletion. Therefore, control littermates and Treg-depleted mice were challenged with an acute 4°C cold exposure after adaptation to room temperature (22°C). In line with previous studies [7], administration of DT to these animals resulted in the rapid systemic depletion of Foxp3-expressing cells (Fig. 2A).


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)

Treg cell depletion and metabolic phenotyping.(A) Real-time RT-PCR analysis of FoxP3 expression in brown adipose tissue (BAT) and spleen in Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice. (B) Oxygen consumption, (C) food intake and (D) locomotor activity during 4 consecutive days at 22°C and 4°C. Injections of vehicle (PBS) or diphtheria toxin (DT) were performed at day 2 and day 3. Values are mean ± SD (n = 9–10); *P<0.05 (Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0118534.g002: Treg cell depletion and metabolic phenotyping.(A) Real-time RT-PCR analysis of FoxP3 expression in brown adipose tissue (BAT) and spleen in Treg cell-proficient (PBS) and Treg cell-deficient (DT) mice. (B) Oxygen consumption, (C) food intake and (D) locomotor activity during 4 consecutive days at 22°C and 4°C. Injections of vehicle (PBS) or diphtheria toxin (DT) were performed at day 2 and day 3. Values are mean ± SD (n = 9–10); *P<0.05 (Student’s t-test).
Mentions: To next test the impact of Treg cells on systemic energy expenditure under cold conditions, we performed deep metabolic phenotyping of Treg-proficient and Treg-deficient mice. Due to the lack of fat-specific Treg targeting systems to date, we employed transgenic mice expressing the diphtheria toxin (DT) receptor under the control of Foxp3 gene regulatory elements [19]. Given the development of systemic immune dysfunction two weeks after DT administration in these animals [19], we restricted our analysis to the adaptation of systemic metabolism to an acute cold challenge and analyzed 48 h after Treg depletion. Therefore, control littermates and Treg-depleted mice were challenged with an acute 4°C cold exposure after adaptation to room temperature (22°C). In line with previous studies [7], administration of DT to these animals resulted in the rapid systemic depletion of Foxp3-expressing cells (Fig. 2A).

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