Basophil-derived IL-4 plays versatile roles in immunity

Abstract

Recent studies demonstrated that basophils play crucial and non-redundant roles in the immune system, in spite of the fact that they are the rarest granulocytes and represent less than 1 % of peripheral blood leukocytes. In response to various stimuli, basophils release effector molecules stored in their cytoplasmic granules, including chemical mediators and proteases, and also secrete cytokines and chemokines. In this review, we will focus on the physiological and pathological roles of basophil-derived IL-4. Basophils can readily produce large quantities of IL-4 and are therefore the important source of IL-4. Basophil-derived IL-4 has been shown to regulate other immune cells, including T cells, B cells, group 2 innate lymphoid cells, monocytes, and macrophages. It also acts on non-hematopoietic cells such as fibroblasts and endothelial cells. Those cells stimulated with basophil-derived IL-4 contribute to the positive or negative regulation of a variety of immune responses in health and disease, including protection against parasitic and bacterial infections, allergy, and autoimmune diseases. Thus, basophil-derived IL-4 plays versatile roles in immunity.

Recent advances in understanding basophil‐mediated Th2 immune responses

“…Although the initial source of IL‐4 still remains uncertain, basophils are proposed as a provider of initial IL‐4 that primarily induces Th2 cell differentiation . Indeed, basophils can readily secrete larger quantities of IL‐4 with lower threshold for activation than do Th2 cells on a per cell basis, in response to a variety of stimuli such as IgE plus allergens . Recent studies have identified versatile roles for basophil‐derived IL‐4 in immune responses, through its action on a variety of immune and non‐immune cells, including T cell, B cells, innate lymphoid cells, monocytes, macrophages, and fibroblasts …”

“…In turn, IL‐4 secreted by basophils conjugated with T cells efficiently promotes T cell differentiation toward Th2 cells. Other stimuli, including IgE plus allergens, IL‐33, and Toll‐like receptor ligands, may also induce IL‐4 production by basophils . In addition to IL‐4 production, basophils appear to have characteristics favorable for Th2 induction.…”

“…49,50 Indeed, basophils can readily secrete larger quantities of IL-4 with lower threshold for activation than do Th2 cells on a per cell basis, in response to a variety of stimuli such as IgE plus allergens. 51,52 Recent studies have identified versatile roles for basophil-derived IL-4 in immune responses, through its action on a variety of immune and non-immune cells, including T cell, B cells, innate lymphoid cells, monocytes, macrophages, and fibroblasts. 52 Macrophages show phenotypic heterogeneity and exhibit distinct features, depending on immunological conditions.…”

“…51,52 Recent studies have identified versatile roles for basophil-derived IL-4 in immune responses, through its action on a variety of immune and non-immune cells, including T cell, B cells, innate lymphoid cells, monocytes, macrophages, and fibroblasts. 52 Macrophages show phenotypic heterogeneity and exhibit distinct features, depending on immunological conditions. 53 Alternatively activated macrophages, also called M2 macrophages, are elicited by canonical Th2 cytokines IL-4 and IL-13, and are generally thought to play a regulatory role in the immune system.…”

Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

“…Basophils rapidly secrete larger quantities of IL-4 than Th2 cells on a per cell basis in response to a variety of stimuli (15). IL-4 has an important role in promoting the differentiation of naive T cells to Th2 cells (16).…”