IL-4

What is IL-4?

IL-4 is a cytokine that is primarily produced by T cells, natural killer T cells, mast cells, and eosinophils. The cytokine is involved in multiple biological functions. IL-4 exerts potent inhibitory activity on macrophages and inhibits the production of many pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 by macrophages. IL-4 regulates B cell growth and immunoglobulin secretion. It has been shown to increase the expression of major histocompatibility complex (MHC) class II and Fcϵ receptor molecules on murine B cells and promote secretion of IgE and IgG1 by B cells. Furthermore, IL-4 was also shown to regulate the proliferation and activity of T cells. IL-4 can promote the growth of T cells and effectively induce the cytolytic activity of T cells. IL-4 induces the differentiation of naive CD4⁺ T cells into TH2 cells which can secrete the cytokines IL-4, IL-5, and IL-10 upon activation. IL-4 has been revealed to be associated with the progression of certain immune disorders, including allergies and some autoimmune diseases, tumors, HIV infections. In humans, the increased level of IL-4 is usually found in the microenvironment of tumors, including renal cell cancer, prostate cancer, colon cancer, non-small cell lung cancer, and breast cancer.

Roles of IL-4-producing γδ T cells

Several studies have reported that γδ T cells are able to produce IL-4 both in vivo and ex vivo. A study showed IL-4-producing γδ T cells, especially CD4⁺ γδ T cells can promote the production of IgE by B cells. In mice models, the increased percentage of CD4+ γδ T cells is associated with elevated IgE levels. Furthermore, γδ T cells have been also indicated to regulate systemic antibody levels in non-immunized mice, including all major subclasses and especially IgE antibodies, through affecting IL-4 production, B-cell activation, and B-cell tolerance. Also, in allergic asthma, γδ T cells including Vγ1.1-bearing γδ T cells are responsible for allergic airway inflammation by producing IL-4 and thus inducing IL-4-dependent IgE and IgG1 responses.

Fig.1 Itk null CD4⁺ γδ T cells secrete IL-4 and induced B-cell class switch to IgE. (Qi, 2009)

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Reference

1. Qi, Q.; et al. Enhanced development of CD4⁺ γδ T cells in the absence of Itk results in elevated IgE production. Blood. 2009, 114(3): 564-571.