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Review
. 2019 Mar 6;20(5):1142.
doi: 10.3390/ijms20051142.

Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications

Luigi Cari  1 , Francesca De Rosa  2 , Giuseppe Nocentini  3 , Carlo Riccardi  4
Affiliations
Review

Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications

Luigi Cari et al. Int J Mol Sci. .

Abstract

Glucocorticoids (GCs) are widely used to treat several diseases because of their powerful anti-inflammatory and immunomodulatory effects on immune cells and non-lymphoid tissues. The effects of GCs on T cells are the most relevant in this regard. In this review, we analyze how GCs modulate the survival, maturation, and differentiation of regulatory T (Treg) cell subsets into both murine models and humans. In this way, GCs change the Treg cell number with an impact on the mid-term and long-term efficacy of GC treatment. In vitro studies suggest that the GC-dependent expansion of Treg cells is relevant when they are activated. In agreement with this observation, the GC treatment of patients with established autoimmune, allergic, or (auto)inflammatory diseases causes an expansion of Treg cells. An exception to this appears to be the local GC treatment of psoriatic lesions. Moreover, the effects on Treg number in patients with multiple sclerosis are uncertain. The effects of GCs on Treg cell number in healthy/diseased subjects treated with or exposed to allergens/antigens appear to be context-dependent. Considering the relevance of this effect in the maturation of the immune system (tolerogenic response to antigens), the success of vaccination (including desensitization), and the tolerance to xenografts, the findings must be considered when planning GC treatment.

Keywords: Treg cell number modulation; desensitizing treatment; glucocorticoids; human allergic diseases; human autoimmune diseases; peripherally derived Treg (pTreg) cells; regulatory T (Treg) cells; thymus-derived Treg cells (tTreg); tolerogenic response.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of in vitro glucocorticoid (GC) treatment on activated T cells. Red arrows indicate lower levels of apoptosis as compared to conventional T cells; green arrows indicate increased cytokine production, proliferation, and differentiation.
Figure 2
Figure 2
Key signaling molecules determining Treg cell survival/expansion/differentiation. The figure summarizes the key mechanisms by which GC treatment increases the number of Treg cells, which are described in detail in Section 8 of this review. Mechanisms include the increased expression by Treg cells of anti-apoptotic signals (upper panel), and the modulation of pathways in naïve T cells (middle panels) and non-T cells (lower panel). Red arrows indicate decreased expression and inhibition; green arrows indicate increased expression and activation.
See this image and copyright information in PMC

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