Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

Abstract

ObjectiveEosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice.DesignAcute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy.ResultsEosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration.ConclusionsEosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators.

Anti- Versus Pro-Inflammatory Metabololipidome Upon Cupping Treatment

“…10S,17S-DiHDoHE, 17R-RvD1 and RvD5 belong to SPM [26, 34] and 14S-HDoHE is a precursor to maresin 1, another SPM [35]. Although we did not observe significant change in IL-6 and TNF-α production from RAW264.7 cells after these SPM treatment for 12 hrs, 14S-HDoHE, 7R-RvD1 and RvD5 showed their anti-inflammatory function in LPS-stimulated BM macrophages.…”

“…3C). It has been acknowledgeable that 14, 15-EET [23], 5, 6-EET [24], 5, 6-DHET [25], 10S,17S-DiHDoHE[26], 17R-RvD1 [27], RvD5 [27] and PGE 1 [28] are anti-inflammatory while 12-HETE is pro-inflammatory [29]. Together these results showed that cupping treatment increased anti-inflammatory lipids and decreased pro-inflammatory lipids.…”

“…10S,17S-DiHDoHE was reported to reduce the severity of colitis via attenuating neutrophil infiltration and decreasing levels of pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6)[26]. 17R-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human PMN migration [36].…”

Eosinophils in mucosal immune responses

“…Moreover, eosinophil levels positively correlate with disease severity in these patients 148 . Additionally, deficiency in MBP 149 , eotaxin-1 24 or eosinophils themselves 150 protects against experimental murine models of colitis, although not in all cases 151 . Eosinophils also have important roles in the remodeling and fibrosis that occur in ulcerative colitis, as eosinophil depleted mice have protection from spontaneous ileitis and tissue remodeling 152 .…”

A Player and Coordinator: The Versatile Roles of Eosinophils in the Immune System

“…Secondly, recent studies have shown that eosinophils in lamina propria are able to induce the differentiation of regulatory T (Treg) cells by producing TGF-β1 and all-trans retinoic acid (ATRA) [46]. Moreover, in mouse models of acute peritonitis or acute colitis, eosinophil-deficient mice developed significantly more severe inflammation than wild-type mice, which suggests that eosinophils play protective roles in terminating acute inflammation, possibly due to their production of the anti-inflammatory lipids such as protectin D1 (PD1) [47,48].…”