Immunopathology alters Th17 cell glucocorticoid sensitivity

Abstract

Th17 cells contribute to several inflammatory conditions and increasing evidence supports that Th17 cells are glucocorticoid resistant. However, Th17 cells in psoriasis and related diseases are glucocorticoid sensitive. We compare glucocorticoid sensitive and resistant immunological diseases and suggest that several aspects in Th-17 related diseases alter glucocorticoid sensitivity of Th17 cells. We identify molecular pathways that are implicated in glucocorticoid sensitivity of Th17 cells in the literature, as this information is useful for developing approaches to overcome glucocorticoid-resistant immunopathology.

Innate immunity in allergy

“…IL‐1β is critically involved in Th17 cell differentiation, production of Th17‐associated cytokines, and neutrophilic inflammation . In addition to the Th2 response, a Th17 response is associated with asthma, notably severe glucocorticoid‐resistant asthma . From various studies of human diseases and mouse models, the elevation of IL‐1β and IL‐18 is associated with the development of allergic diseases, such as asthma, dermatitis, rhinitis, and conjunctivitis .…”

Glucocorticoids promote intrinsic human TH17 differentiation

“…However, human T H 17 responses to glucocorticoids are not homogeneous, showing a clear influence of the pathophysiologic context. 1 In patients with psoriasis, for example, T H 17 cells are successfully suppressed by GCs, whereas in patients with lupus erythematosus, T H 17 cells are refractory to glucocorticoid treatment. Furthermore, glucocorticoid use has been repeatedly reported to be associated with increased IL-17 levels in so-called refractory diseases, and one study on patients with lupus erythematosus provided evidence that glucocorticoids, but not other systemic therapies, are directly linked to increased T H 17 responses.…”

Cellular reactions of CD3+ CD4+ CD45RO+ T-lymphocytes on dexamethason in in normal patients and in patients with with rheumatoid arthritis in vitro

“…Дан-ные литературы в отношении ýффектов ГК на продукцию IL-17 Т-клетками крайне противоре-чивы. Согласно одним источникам, клоны Th17 устойчивы к супрессорному влиянию ГК; более того, ГК опосредуют дифференцировку клеток Th17 in vitro [24,37]. Тогда как другими исследо-вателями были получены прямо противополож-ные данные [38].…”

“…M. Noack (2016) описан ингибиторный ýффект ГК в отношении продукции IL-17 in vitro в смешанной культуре периферических клеток крови и синовиоцитов, полученной у больных РА [40]. Также выявлено супрессорное действие ГК на содержание Th17-клеток на периферии и их секрецию IL-17 при активной фазе РА [37]. В ýксперименте с использованием нокаутных мы-шей было показано, что IL-17 является одним из основных таргетных медиаторов воспаления (при моделировании РА) для действия ГК [41].…”