Transtracheal Instillation of Anti-TSLP Antibody Alleviates Airway Inflammation and Airway Hyperresponsiveness in OVA-Induced Asthma Model Mice

Abstract BackgroundThymic stromal lymphopoietin (TSLP) is a mainly epithelial cell-derived cytokine that may be important in initiating T2 allergic inflammation. Anti-TSLP antibody inhibit allergic inflammation. Previous animal studies have evaluated the anti-allergic efficacy of injecting anti-TSLP antibody intraperitoneally, subcutaneously, or intravenously. However, transtracheal instillation, a less invasive route for anti-TSLP antibody administration, is hitherto unstudied. This study evaluates the efficacy of transtracheally instilling anti-TSLP antibody in inhibiting airway inflammation and hyperresponsiveness in OVA-induced asthma model Balb/c mice.MethodsBalb/c mice were randomly divided into four groups: the control group, the OVA-induced asthma model group, the anti-TSLP mAb treatment group (TSLP mAb group), and the IgG2a mAb control group (IgG2a mAb group). Each group contained nine to eleven mice. Mice in the asthma model group were sensitized with OVA to trigger allergic responses and were treated with transtracheal instillation of normal saline. Mice in the TSLP mAb group received transtracheal instillation of anti-TSLP mAb, while mice in the IgG2a group received transtracheal instillation of IgG2a mAb. Both of these groups were then subjected to OVA challenge. Airway responsiveness was measured as an enhanced pause (Penh) using noninvasive plethysmography. The severity of inflammation was evaluated by histopathological examination using the Underwood assessment of the lung sections. Changes in expression of TSLP, TSLP receptor (TSLPR), T-box transcription factor (T-bet), GATA binding protein 3 (GATA3) and forkhead box protein P3 (Foxp3) were assessed using RT-PCR and immunohistochemical staining. ResultsAirway hyperresponsiveness and infiltration of airway inflammatory cells in the TSLP mAb group were significantly reduced, compared with the OVA and the IgG2a mAb groups. Meanwhile，TSLP, GATA3 mRNA expression and GATA3 protein levels were significantly decreased in the TSLP mAb group, compared with the OVA and the IgG2a mAb groups (P＜0.05）. No significant differences were observed in either T-bet or Foxp3 in the lung section of mRNA and protein expression among these four groups (P＞0.05).ConclusionTranstracheal instillation of anti-TSLP antibody attenuated lung inflammation and airway hyperresponsiveness in OVA-induced asthmatic mice, possibly through downregulation of perivascular and peribronchiolar lymphocytes, neutrophils and GATA3 expression in the airway.