Interleukin 9 promotes influx and local maturation of eosinophils

Abstract

The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5-driven eos maturation of precursors.

Absence of bacterially induced RELMβ reduces injury in the dextran sodium sulfate model of colitis

“…Murine recombinant RELMβ (2 μg in 100 μl PBS; PeproTech) was injected i.p. into BALB/c mice, followed by peritoneal lavage after 1, 24, 48, and 72 hours as described previously (47). The vehicle control was spiked with 5 pg of LPS from E. coli (Sigma-Aldrich) to approximate the amount of endotoxin in the recombinant RELMβ, less than 2.5 pg/μg, measured by limulus assay.…”

“…Total RNA was isolated from cells of the peritoneal lavage 1 hour after injection of RELMβ (0.5 μg in 100 μl PBS), and TNF-α mRNA expression was determined by quantitative RT-PCR analysis (as described above). The morphological changes in macrophages, 24 hours after RELMβ administration, were assessed on cytospin preparations stained by Shandon Kwik-Diff (Thermo Electron Corp.), and total and differential cell counts were determined as described previously (47). Two hundred cells were counted for each of the cytospin slides under immersion oil, using a Nikon light microscope (at ×1,000 magnification).…”

Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma

“…8,9,13,25,26 Both mast cells and eosinophils are implicated in the stimulation of HRS cells, 4,18 and the number of these cell types in affected lymph nodes correlates with poor prognosis. [27][28][29] Thus, IL-9 may be of importance in HL development, regulating both HRS cells as well as infiltrating cells.…”

“…10 In HL tumours, IL-9 is also believed to work in a paracrine fashion, stimulating and activating the infiltrating T H 2 type of lymphocytes. Interactions with other cells constituting the tumours such as mast cells, 9,11 monocytes 12 and eosinophils 13 are also plausible.…”

IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic Development

“…41). The ability of peripheral NKT cells to specialize in distinct functional subsets has been controversial (11,(35)(36)(37)(38). However, Foxp3 expression and acquisition of B cell helper capacity are not found in naive mice, but arise upon immunization (16)(17)(18)(19).…”