IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation

Abstract

Interleukin-2 (IL-2) is a pleiotropic cytokine that drives T-cell growth, augments NK cytolytic activity, induces the differentiation of regulatory T cells, and mediates activation-induced cell death. Along with IL-4, IL-7, IL-9, IL-15, and IL-21, IL-2 shares the common cytokine receptor γ chain, γc, which is mutated in humans with X-linked severe combined immunodeficiency. Herein, we primarily focus on the recently discovered complex roles of IL-2 in broadly modulating T cells for T helper cell differentiation. IL-2 does not specify the type of Th differentiation that occurs; instead, IL-2 modulates expression of receptors for other cytokines and transcription factors, thereby either promoting or inhibiting cytokine cascades that correlate with each Th differentiation state. In this fashion, IL-2 can prime and potentially maintain Th1 and Th2 differentiation as well as expand such populations of cells, whereas it inhibits Th17 differentiation but also can expand Th17 cells.

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

“…Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Although it is historically assumed that high testosterone induces prostate overgrowth, most observational studies failed to find correlations between circulating testosterone levels and BPH: in fact, no clear correlation with serum PSA or prostate volume across the normal testosterone range has been shown (Liu et al 2007). In addition, the notion that intraprostatic 5a-reductase activity, which is responsible for converting the bulk of testosterone into DHT, is altered in the BPH tissues is contentious (Isaacs et al 1983, Bartsch et al 1990).…”

“…This suggests that DHT could play a broad antiinflammatory role on CD4 C T helper cells. Moreover, DHT inhibited the production of IL2, T-cell growth and differentiation (see Liao et al (2011)), thus explained the reduced proliferation of CD4 C T cell clones in culture with DHT-primed hBPH cells.…”

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

“…Measuring the activation of T cells stimulated in the presence or absence of MSCs in vitro is a commonly used assay for assessing the effects of stimulatory and inhibitory factors on MSC-mediated immune suppression; however, this approach is rarely used to compare the inherent immunosuppressive capacity of MSC lines, and interexperimental variability can make it difficult to reliably distinguish between MSC lines with similar immunosuppressive capacities (5). Although T-cell proliferation is often used to measure activation in MSC immunosuppression studies, other measures of activation such as cytokine secretion and up-regulation of growth factor receptors like CD25 more directly assess activated T-cell effector functions (25,26). In this study, we assessed cytokine secretion (IFN-γ and TNF-α) and CD25 expression in addition to proliferation in both CD4 + and CD8 + T cells activated in the presence of MSCs (Fig.…”

miR-155 augments CD8 + T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γ c cytokines

“…Because miR-155 does not affect the expression of the IL-15 and IL-7 receptor complexes (21), we focused on downstream signaling. It is well established that γ c cytokines primarily signal through three pathways: Mapk, Jak3/ Stat5, and PI3K/Akt (27). To determine whether any of these pathways were modulated by miR-155 overexpression, we evaluated the amount of phosphorylated Mapk1, Akt, and Stat5 in miR-155 and Ctrl cells.…”