Down-Regulation of Restores Th17/Treg Immune Balance and Alleviates Airway Hyperviscosity in Asthmatic Mice via Inactivation of STAT3 Pathway.

BACKGROUND

Allergic asthma (AA) is a prevalent chronic airway inflammation disease. In this study, this study aims to investigate the biological functions and potential regulatory mechanisms of the insulin receptor () in the progression of AA.

METHODS

BALB/c mice (n = 48) were randomly divided into the following groups: control group, AA group, AA+Lentivirus (Lv)-vector short hairpin RNA (shRNA) group, AA+Lv-vector group, AA+Lv- shRNA group, and AA+Lv- group. The pulmonary index was calculated. mRNA and protein expression levels of , signal transducer and activator of transcription 3 (STAT3), Janus kinase 2 (JAK2), phosphorylated-STAT3 (p-STAT3), phosphorylated-JAK2 (p-JAK2), alpha-smooth muscle actin (), febrile neutropenia (), mucin 5AC (), and mucin 5B () were examined using reverse-transcription quantitative PCR (RT-qPCR) and western blot assays. Positive expressions of , retinoic acid-related orphan receptor gamma-t (RORγt), and forkhead box protein P3 (Foxp3) were quantified by immunohistochemistry. Fluorescence intensities of α-SMA and FN were detected by immunofluorescence. Pathological morphology was observed through hematoxylin-eosin (H&E) staining, Masson staining, and Periodic Acid-Schiff (PAS) staining. Contents of immunoglobulin E (IgE), interleukin-6 (IL-6), eotaxin, interleukin-4 (IL-4), interleukin-13 (IL-13), interferon-γ (IFN-γ), interleukin-17 (IL-17), and interleukin-10 (IL-10) were quantified using enzyme-linked immunosorbent assay (ELISA). The percentage of T helper 17 (Th17) and regulatory T (Treg) cells was determined through flow cytometry.

RESULTS

Compared to the control group, expression levels of , p-STAT3, p-JAK2, , , , , RORγt, and Foxp3, as well as IgE, IL-6, eotaxin, IL-4, IL-13, and IL-17 contents, pulmonary index, glycogen-positive area (%), and Th17 cell percentage significantly increased ( < 0.05). Additionally, pulmonary histopathological deterioration and collagen deposition were aggravated, while Treg cell percentage and IFN-γ and IL-10 contents remarkably decreased ( < 0.05). The overexpression of further exacerbated the progression of allergic asthma, but the down-regulation of reversed the trends of the above indicators.

CONCLUSIONS

The down-regulation of alleviates airway hyperviscosity, inflammatory infiltration, and airway remodeling, restoring Th17/Treg immune balance in AA mice by inactivating the STAT3 pathway.