IL-3 Induces Basophil Expansion In Vivo by Directing Granulocyte-Monocyte Progenitors to Differentiate into Basophil Lineage-Restricted Progenitors in the Bone Marrow and by Increasing the Number of Basophil/Mast Cell Progenitors in the Spleen

Abstract

Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL-3 plus anti-IL-3 Ab) greatly facilitated the differentiation of GMPs into basophil lineage-restricted progenitors (BaPs) but not into eosinophil lineage-restricted progenitors or mast cells in the bone marrow. We also found that the IL-3 complex treatment resulted in ∼4-fold increase in the number of basophil/mast cell progenitors (BMCPs) in the spleen. IL-3-driven basophil expansion depended on STAT5 signaling. We showed that GMPs but not common myeloid progenitors expressed low levels of IL-3 receptor. IL-3 receptor expression was dramatically up-regulated in BaPs but not eosinophil lineage-restricted progenitors. Approximately 38% of BMCPs expressed the IL-3Rα-chain. The up-regulated IL-3 receptor expression was not affected by IL-3 or STAT5. Our findings demonstrate that IL-3 induced specific expansion of basophils by directing GMPs to differentiate into BaPs in the bone marrow and by increasing the number of BMCPs in the spleen.

Serum IgE clearance is facilitated by human FcεRI internalization

“…Next, we increased the frequency of basophils in a separate group of 10:90 (Tg + /Tg -) mixed chimeric mice by injecting IL-3/ anti-IL-3 antibody complexes. As shown in previous studies (39,40), this treatment increased the frequency of basophils by approximately 8-fold but did not increase the frequency of monocytes or DCs ( Figure 7G). Furthermore, the rate of serum IgE clearance was not accelerated by injection of IL-3/anti-IL-3 antibody complexes ( Figure 7H).…”

STAT5 in human basophils: IL‐3 is required for its FcεRI‐mediated phosphorylation

“…It has been disclosed that STAT5 is essential for development and expansion of both murine mast cells and basophils (11)(12)(13). An important activator of STAT5 in these cells is interleukin (IL)-3, which plays a fundamental role in mast cell and basophil biology (14,15).…”

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

“…37 IL-3, a cytokine that induces the differentiation of basophils and mast cells, 38 has previously been shown to expand basophils in vivo without affecting the number of tissue mast cells. 27 Although previous studies have emphasized IL-3C-mediated basophil expansion, 27 our experiments demonstrated a dramatic increase in both basophils and eosinophils in the peripheral blood as well as in the AD-like skin lesions in the IL-3C-treated mice (Figure 2a, Supplementary Figures S2 and S3). These results confirmed the specificity of IL-3C-induced basophil and eosinophil expansion by showing that mice that received IL-3C treatment were comparable to normal mice in terms of the cell counts of mast cells in the peritoneum and ear tissue and the blood cell counts of neutrophils, monocytes, T cells, and B cells (Supplementary Figure S3).…”

“…27 Briefly, 200 ng/mouse of recombinant mouse IL-3 (Peprotech Inc., Rocky Hill, NJ, USA) was incubated with 1 mg/mouse of rat anti-mouse IL-3 antibody (Biolegend Inc., San Diego, CA, USA) for 15 min at room temperature to form IL-3C, which was subsequently injected intraperitoneally (i.p.) into the mice every other day for 14 days (day 0-14, eight times in total).…”