Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils

Abstract

Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific α-subunit of the IL-9 receptor (IL-9R–α). The expression of IL-9R–α by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase–polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34+cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34+ cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R–α. IL-9 also up-regulated the IL-5R–α chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5–mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

Granule protein changes and membrane receptor phenotype in maturing human eosinophils cultured from CD34+ progenitors

“…These actions are mediated via a membrane-bound IL-5Ra that is composed of a ligand-speci®c a-subunit chain and a common a-chain. Our results demonstrate that both IL-5Ra and IL-9Ra are expressed by CE early in their development (days 7, 14), ®ndings that in most respects are in agreement with those of Gounni et al [24]. Furthermore, the expression of IL-5Ra and IL-9Ra showed signi®cantly greater variation in the range of mean¯uorescence compared with PBE.…”

Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology

“…A potentially important role of IL-9 in the pathogenesis of asthma has been supported recently by multiple findings that have revealed the pleiotropic effects of IL-9 on various cell types associated with allergic asthma, including mast cells, B cells, eosinophils, and airway epithelial cells. Studies in humans and animals have shown the involvement of IL-9 in lung eosinophilia, mucus hypersecretion, Ig production, and pulmonary mastocytosis (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These findings have been strongly supported by our studies with transgenic mice that constitutively express IL-9 selectively within their lungs (21).…”

“…It was suggested that IL-9 would exert its function by acting directly on eosinophils. It has been shown in vitro and in vivo that IL-9 was able to upregulate IL-5Rα expression on human eosinophils that could potentiate differentiation, maturation, and survival of eosinophils through the action of IL-5 (13,17). From the studies presented here, we conclude that in our system the development of lung inflammation, especially eosinophilia, requires further signals, in addition to IL-9, which can only be provided by IL-13.…”

Estradiol administration controls eosinophilia through estrogen receptor-α activation during acute peritoneal inflammation

“…In addition, eosinophil apoptosis, which occurs as part of the normal resolution process of inflammation, appears to be delayed by survival factors produced by neighboring cells or by eosinophils themselves [56]. For instance, IL-5, as well as IL-9, could directly impact on eosinophilia by enhancing their mobilization from the BM but also by favoring their survival in the inflamed tissues [29,[45][46][47]. Moreover, IL-25 is also considered as a key regulator to initiate tissue eosinophilia in response to allergen challenge [57] and helminth infections [49,58,59] by enhancing the expression of type 2 cytokines, such as IL-5 and IL-13 [48,49,57].…”

“…During inflammatory responses, the release of prosurvival factors, such as IL-5 and IL-9, plays a crucial role by promoting eosinophilia through BM production and mobilization but also by counteracting proapoptotic signals in eosinophils [29,[45][46][47]. At early time-points following TGC injection, the peritoneal ( Fig.…”