Role of Tissue-Localized Regulatory T Cells in Health and Disease

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Background

Tissue-specific immunological processes control treatment outcomes in autoimmunity, inflammation and cancer. Regulatory T cells (Tregs) in non-lymphoid tissues and lymphoid organs share a common Foxp3+CD4+ precursor. However, tissue Tregs, depending on the microenvironment, are specialized to express unique molecular programs and display unique T cell receptor repertoires, which enables them to survive in a variety of microenvironments and to exert diverse immunological and non-immunological regulatory functions. Tregs in adipose tissue , muscle, skin, gut, lung, liver and central nervous system have been shown to orchestrate common and tissue-specific functions.

This Research Topic aims to advance the field by collecting papers that provide new insights into the actions of tissue Tregs. Dissecting the physiologic function of these cells has the potential to inform the design of more precise, effective and safe therapeutics for a number of pathologies. Understanding the action of tissue Tregs in comparison with circulating Tregs requires a deep understanding of genes/pathways in healthy and disease states. New technologies, including high-resolution transcriptomics and imaging, are being applied to gain further insights in order to draw new paradigms. In addition, while mouse models are frequently used to study tissue immunology, evolutionarily distinct mechanisms might be in action in human tissues. This Topic will explore such similarities and differences.

We welcome manuscripts that describe novel functions of various tissue-Treg populations. It is unclear what cellular networks are driving tissue adaptation in healthy or disease states. Topics of interest include, but are not limited to:

• The use of genetic models, high-resolution gene-expression methodologies, multiplex imaging, TCR repertoire analysis and/or antigen-display libraries to characterize tissue-Treg populations, exploring heterogeneity both between and within non-lymphoid tissues
• Elucidation of the nature of antigens and TCR repertoires involved in tissue-Treg adaptation
• Novel, tissue-adapted, Treg effector mechanisms and survival factors
• Identification of cell types that tissue Tregs interact with to regulate local tissue homeostasis -- and the molecular programs involved
• Papers that aim to enhance our understanding of human tissue Tregs, highlighting both similarities to and differences from their murine counterparts
• What can we learn from tissue-Tregs in non-human, non-murine models?




Dr. Ali Zarrin is an employee of TRex Bio, involved in the identification of novel therapeutics for the treatment of immune-mediated diseases.

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