Metabolic disorders are increasingly threatening global health, demanding urgent exploration of innovative strategies for prevention and treatment. Recently, the intricate interplay between immune cells and metabolic tissues (e.g., adipose tissue or skeletal muscle), has caught attention. Particularly noteworthy are regulatory T cells (Tregs), a type of immune cell that not only governs immune functions but also influences the maintenance, integrity, and regeneration of tissues. In this regard, the non-canonical roles of Tregs and their impact on tissue homeostasis and function underscore the potential for niche-specific targeting of these cells in addressing metabolic diseases.
Researchers from the Type 1 Diabetes Immunology Research Unit have now compiled the latest insights into niche-specific control of tissue function by Tregs, as published in Cell Metabolism in a special issue on the prevention of metabolic disease. In this review perspective, Carolin Daniel's group delves into the challenges and prospects of Treg-mediated control of metabolic tissues, emphasizing the functional specialization of tissue-resident Tregs. Recent studies highlight the crucial role of tissue residing Tregs, particularly in metabolic tissues like adipose tissue, in preserving proper metabolic function and regulating systemic metabolism. Obese adipose tissue is characterized by a loss of Tregs that drives metabolic impairments and insulin resistance. Significantly, Treg expansion has proven to be effective in preventing and even reversing insulin resistance in obesity.
Moreover, in the context of skeletal muscles, Daniel’s group as part of the TRR355 (transregional collaborative research center 355 – Heterogeneity and Functional Specialisation of Regulatory T Cells in Distinct Microenvironments) and of the German Center for Diabetes Research (DZD) at Helmholtz Munich together with DZD researchers of the German Institute of Human Nutrition in Potsdam-Rehbrücke (DIfE) has recently shown that exercise promotes a stable induction of highly functional muscle-residing Tregs, shedding light on the molecular interface connecting Treg-based regulation with muscle function and regeneration).
In summary, Tregs in metabolic tissues display distinct characteristics compared to their counterparts in lymphoid organs, playing a critical role in maintaining metabolic balance, preventing inflammation, and controlling tissue function and regeneration in metabolic diseases. Further research efforts have the goal to provide a deeper understanding of Treg cell heterogeneity and their tissue specific functions. These insights into niche-specific Tregs will allow to explore their potential for developing precision immune therapies that target not only (auto)immune reactions and chronic inflammation but also foster tissue regeneration and repair in metabolic diseases.
Publication:
Becker, M.*, Dirschl, S.M.*, Scherm, M., Serr, I., Daniel, C. Niche-specific control of tissue function by regulatory T cells – current challenges and perspectives for targeting metabolic disease. Cell Metabolism (2024), https://doi.org/10.1016/j.cmet.2023.12.019
Link to related publication:
Becker et al., Regulatory T cells require IL6 receptor alpha signaling to control skeletal muscle function and regeneration. Cell Metabolism (2023). https://doi.org/10.1016/j.cmet.2023.08.010
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*Funding information: Related research is funded by the German Center for Diabetes Research (DZD) and by the Deutsche Forschungsgemeinschaft (DFG, project numbers 490846870-TRR355/1 TPA02 and TPB02).
