Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice

Abstract

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed‐type hypersensitivity and collagen‐induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin‐induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro‐inflammatory and anti‐inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T‐bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down‐regulation of Th2 response and the up‐regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases.

Schistosome Infection and Schistosome-Derived Products as Modulators for the Prevention and Alleviation of Immunological Disorders

“…These data revealed a novel immune protective mechanism involving T cell epitopes from helminth-derived Th1-inducing antigens in modulating allergic asthmatic responses through an enhancing Th1 response ( 39 ). Also, the aforementioned peptide, SJMHE1, suppressed airway inflammation in the OVA-induced allergic asthma mouse model with modulation of pro- and anti-inflammatory cytokines in splenocytes and lungs, and decreased numbers of infiltrating inflammatory cells and eosinophils ( 40 ). SJMHE1 treatment during OVA sensitization and challenge in BALB/c mice significantly reduced the IL‐4 mRNA level in the splenocytes, suppressed the expression of IL‐4, IL‐5, and IL‐17 mRNA in the lungs, and increased IFN‐γ, IL‐10, and IL‐35 mRNA, indicating the suppressive effect was likely associated with decreased populations of Th2 and Th17 cells and an increased frequency of Th1 and Treg cells ( 40 ).…”

“…Also, the aforementioned peptide, SJMHE1, suppressed airway inflammation in the OVA-induced allergic asthma mouse model with modulation of pro- and anti-inflammatory cytokines in splenocytes and lungs, and decreased numbers of infiltrating inflammatory cells and eosinophils ( 40 ). SJMHE1 treatment during OVA sensitization and challenge in BALB/c mice significantly reduced the IL‐4 mRNA level in the splenocytes, suppressed the expression of IL‐4, IL‐5, and IL‐17 mRNA in the lungs, and increased IFN‐γ, IL‐10, and IL‐35 mRNA, indicating the suppressive effect was likely associated with decreased populations of Th2 and Th17 cells and an increased frequency of Th1 and Treg cells ( 40 ). While the suppressive mechanism involving the elevation of IL-10 in the allergic asthma mouse is different from that in the CIA model, schistosomes and their products modulate distinct targets regulating Th1/Th2/Th17-associated inflammation in the different models.…”

Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice

“…Briefly, apart from the control group, the mice were sensitized with 40 μg OVA ovalbumin (OVA, Sigma, Poole, UK) and 2 mg 10% aluminum hydroxide (Sigma) in PBS on day 0, 7, and 14 by intraperitoneal injection. From days 21 to 55, the sensitized mice were challenged with aerosolized OVA (5%) for 20 min in PBS as previously described [ 22 ]. Bronchoprovocation was performed in a vented plastic chamber (30 × 20 × 15 cm).…”

“…BALF was collected as previously described [ 22 ]. Briefly, left bronchial tubes of the mice were ligated, and the ice-cold PBS (0.5 mL) was instilled twice into the right lungs.…”

Allergen Specific Treg Upregulated by Lung-stage Schistosome Infection Alleviates Allergic Airway Inflammation via Inhibiting IgE Secretion

“…Moreover, contradictory results were also reported regarding the roles of regulatory T cells in schistosome mediated protection. Some studies showed that Treg was an important effector in schistosome mediated protection against asthma (21,23,(26)(27)(28), while a more recent study showed that the protection was independent of Treg (24).…”