REVIEW: Mechanisms of Glucocorticoid Resistance in Nonclassical T Helper Populations Th17.1/Ex-Th17

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Elena M. Kuklina^1,a*

¹Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, Russia

^* To whom correspondence should be addressed.

Received: November 25, 2024; Revised: January 15, 2025; Accepted: January 20, 2025

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The nonclassical population of Th1-polarized Th17 lymphocytes (Th17.1/ex-Th17) is currently in the focus of researchers’ attention. These cells possess a unique proinflammatory potential and ability to penetrate blood-tissue barriers and play a key role in the pathogenesis of many inflammatory diseases, primarily autoimmune ones. Th1-polarized Th17 lymphocytes prevail in the autoimmune lesion foci and are considered to be a promising therapeutic target in these pathologies. At the same time, recent studies have shown another distinctive feature of Th1-polarized Th17 – their selective resistance to glucocorticoids. Since glucocorticoids are the first-line drugs for the treatment of the autoimmune disease exacerbation, understanding the causes of this phenomenon is crucial for predicting patients’ response to therapy and improving the treatment effectiveness. This review analyzes the mechanisms of drug resistance of Th1-polarized Th17 cells, compares these mechanisms with those typical of nonpathogenic classical Th17 cells, and discusses the role of glucocorticoid resistance in the body’s response to glucocorticoid therapy.

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KEY WORDS: Th17.1, ex-Th17, glucocorticoids, drug resistance, autoimmunity

DOI: 10.1134/S0006297924604222

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