Cutting Edge: IL-5 Primes Th2 Cytokine-Producing Capacity in Eosinophils through a STAT5-Dependent Mechanism

Abstract

Both type-2 CD4+ Th cells (CD4+Th2) and type-2 innate effector cells play critical roles in generating type-2 immunity that can either be protective against parasitic infection or cause tissue damage in allergy and asthma. How innate effector cells acquire the capacity to produce Th2 cytokines is not entirely known. We previously showed that IL-4 induced differentiation of Th2 cytokine-producing eosinophils. To determine whether other Th2 cytokines can also induce Th2 cytokine-producing capacity in innate effector cells, we cultured bone marrow progenitor cells in the presence of various Th2 cytokines. IL-5, but not IL-13 or IL-25, primed bone marrow progenitor cells to differentiate into robust IL-4-producing cells. The majority of IL-4-producing cells induced by IL-5 were eosinophils. Importantly, IL-5 completely depended on STAT5 to promote IL-4-producing capacity in eosinophils. Thus, our study demonstrates that IL-5 functions as a potent factor that drives bone marrow progenitor cells into IL-4-producing eosinophils.

A Phosphosite Screen Identifies Autocrine TGF-β-Driven Activation of Protein Kinase R as a Survival-Limiting Factor for Eosinophils

“…1C). Previously, the phosphorylation of STATS 1, 3, and 5 in IL5-stimulated eosinophils has been described (9,(17)(18)(19). Furthermore, we and others have reported the phosphorylation of Jak1 and Jak2 by IL-5 but not by chemokines (2,9,12,17,20).…”

Marked Induction of c-Maf Protein during Th17 Cell Differentiation and Its Implication in Memory Th Cell Development

“…1B), Maf, Rorc and Rora were all high in Factor 2 but low in Factor 1. In contrast, Gata3, which encodes the master regulator transcription factor of Th2 cells, was very high in Factor 1 but low in Factor 2, and so was Stat5a, which is implicated in Th2 differentiation (29,30). From these data, we may safely call Factor 1 "a Th2-related factor" and Factor 2 "a Th17-related factor".…”

Stat5 Is Essential for Early B Cell Development but Not for B Cell Maturation and Function

“…Gene disruptions of Stat5A and Stat5B in mice have highlighted the important functions of Stat5A and Stat5B in cytokine signaling (19). Studies of the Stat5A/5B ⌬N mice, which retain N-terminally truncated Stat5 proteins, have revealed the critical roles of Stat5A and Sta5B in prolactin-regulated ovarian function (21), hemopoietic stem cell repopulating potential (23)(24)(25), IL-2-induced T cell proliferation (26), IL-3-mediated mast cell development and survival (27), and IL-5-driven differentiation of Th2-type eosinophils (28). However, it is surprising that Stat5A/5B ⌬N mice only have minor disturbance of early B cell progenitors (21,41,42) and a normal number of thymocytes (24,26,43).…”

“…Mice with both Stat5A and Stat5B alleles targeted at the N terminus of the proteins retain N-terminally truncated Stat5 proteins and are hence termed as Stat5A/5B ⌬N . Studies of Stat5A/5B ⌬N mice have illustrated key roles for Stat5A and Stat5B in prolactin-regulated ovarian function (21), the repopulating potential of hemopoietic stem cells (23)(24)(25), IL-2-induced T cell proliferation (26), IL-3-mediated mast cell development and survival (27), and IL-5-driven differentiation of Th2-type eosinophils (28). IL-7 predominantly activates Stat5 (29).…”