IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL-4, and IL-3 Synergizes with IL-4 to Enhance Th2 Cell Differentiation

Abstract

IL-3, a cytokine secreted by activated T lymphocytes, is known to regulate the proliferation, survival, and differentiation of hematopoietic cells. However, the role of IL-3 in regulation of T cell functions is not fully delineated. Previously, we have reported that IL-3 plays an important role in development of regulatory T cells in mice. In this study, we investigated the regulation of IL-3R expression on human Th cells and also examined the role of IL-3 in effector functions of these cells. We found that human peripheral blood Th cells in resting state do not show surface expression of IL-3R; however, its expression was observed at transcript and intracellular protein levels. The functional IL-3R expression on the surface was seen only after antigenic stimulation. When naive Th cells were activated in the presence of various cytokines, we found that IL-4 significantly increases the surface expression of IL-3R and also increases the number of IL-3R + Th cells. Interestingly, IL-3R + cells exhibit a Th2 cell-like phenotype and show high GATA-3 expression. Moreover, Th2 cells in presence of IL-3 show increased expression of type 2 effector cytokines, such as IL-4, IL-5, and IL-13. Furthermore, IL-3R expressing and IL-3-secreting Th cells were high in house dust miteallergic patients. Thus, to our knowledge, we provide the first evidence that the expression of IL-3R on activated human Th cells is modulated by IL-4, and IL-3 regulates the effector functions of Th2 cells. Our results suggest that IL-3 may play an important role in regulating allergic immune responses.

Mechanism of Intestinal Flora and Proteomics on Regulating Immune Function of Durio zibethinus Rind Polysaccharide

“…The Th1 and Th2 subgroups of mice can secrete IL-2 and IL-4, respectively, and both IL-2 and IL-4 can promote the proliferation of T cells [43,44]. In addition, IL-4 can also promote the expression of B cells, enhance the antigen presentation ability of B cells, increase IgG1 and IgE levels, and make the responses of immune system to antigen stimulation [45,46]. Gong et al found that Bletilla baicalensis polysaccharides could significantly enhance the levels of IL-2 and IL-4 in immunosuppressed mice [47] which is similar with the effect of DZMP in this paper.…”

Polysaccharide of atractylodes macrocephala koidz activated T lymphocytes to alleviate cyclophosphamide-induced immunosuppression of geese through novel_mir2/CD28/AP-1 signal pathway

“…Cytokines play a very important role in infection, inflammation, and cancer ( Fu et al., 2018 ; Fan et al., 2019 ; Guo et al., 2019 ; Meng et al., 2019 ). Increased level of IL-3, IL-5, IL-1β, GM-CSF could help active the lymphocytes and promote lymphocytes proliferation( Kumar et al., 2020 ). IL-3, IL-5, and GM-CSF are produced primarily by activated T cells, promote myeloid cell proliferation and differentiation, and play a role in a variety of human diseases, particularly cancer and inflammation( Koh et al., 2010 ).…”

The AP-1 factorsFOSL1andFOSL2co-regulate human Th17 responses

“…For instance, FOSL1 and FOSL2 negatively-regulated Th1-lineage genes (TBX21 109,110 , IFNG 111 , IL12RB2 112 and HOPX 113 ), while promoting the expression of Th2-specific factors (GATA3 114 , IL13 115 and IL3 116 ). It however remains to be understood if these AP-1 factors restrain Th17 responses by modulating helper-T-cell diversification.…”