Regulatory T cells: multifaceted and omnipresent

Abstract. Regulatory T cells (Treg) are key mediators of immune tolerance and tissue homeostasis, preventing autoimmune reactions and excessive inflammation. The main subpopulations are: thymic (tTreg/nTreg), formed in the thymus and enriched in receptors for autoantigens; induced (iTreg/pTreg), differentiating in the periphery from naive CD4⁺ T cells. Phenotypic identification is based on the expression of Foxp3, CD25 and low levels of CD127. Suppression mechanisms include: secretion of inhibitory cytokines (IL 10, TGF β, IL 35); action of checkpoint molecules (CTLA 4, PD 1, LAG 3, TIGIT); metabolic modulation via CD39/CD73 (adenosine generation); suppression of Ca²⁺ signaling in effector lymphocytes, etc. Treg stability is maintained by epigenetic mechanisms and metabolic programs; plasticity is manifested in the formation of hybrid Treg/Th subpopulations with partial suppressor activity and the production of corresponding helper cytokines: Th1-Treg, Th2-Treg, Th17-Treg, Tfr-Treg, depending on the tissue microenvironment. Migration and tissue residency are regulated by chemokine receptors and adhesion molecules. CD69 blocks S1PR1, ensuring Treg retention in tissue. ST2 serves as a marker and functional receptor for Treg in barrier tissues and is activated by "alarm signals" (IL 33). In different organs, Tregs acquire unique transcriptomes and functional characteristics (for example, in the intestine—α4β7⁺CD103⁺; in adipose tissue—dependence on PPARγ, ID2, and BATF). They participate in maintaining tolerance, controlling inflammation, and inducing reparative processes by suppressing inflammation and switching macrophages to the M2 phenotype. Tregs provide protective control of the immune response, but in some cases (tumors, fibrosis) they can contribute to disease progression. Studying the stability, plasticity, and migration of Tregs opens up prospects for targeted immunotherapy.

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