BATF participates in airway inflammation of neutrophilic asthma via regulating Th17 cells activation

Abstract

Neutrophilic asthma (NA) is a common subtype of non-eosinophilic asthma, characterized by the infiltration of neutrophils. Basic leucine zipper transcription factor ATF-like (BATF) is the nuclear transcription factor that initiates lymphocyte differentiation. The mechanism by which BATF affects T cell differentiation leading to neutrophil accumulation in NA lung tissue remains unclear. In this study, we established murine models of NA through sensitization with ovalbumin (OVA) /complete Freund's adjuvant and subsequent challenge with OVA/lipopolysaccharide. Using these models, we systematically investigated pathological alterations, inflammatory cell infiltration patterns, and cytokine expression profiles in murine lung tissues. The impact of glucocorticoid intervention on the pathology of airway inflammation in NA mice was assessed, and the markers associated with lymphocyte differentiation RORγt and FoxP3 were detected. Furthermore, on the basis of BATF knockdown, the distribution of lymphocyte subtypes and the effect on neutrophil activity in the lung tissues of NA mice were observed. Our results revealed that both BATF and IL-17A showed high expression in NA lung tissue, and neutrophils were predominant in bronchoalveolar lavage fluid (BALF). Glucocorticoid treatment failed to alleviate lung histopathological lesion and exacerbated neutrophil accumulation in NA. Inhibiting BATF could significantly reduce neutrophil accumulation, as well as downregulate IL-17A expression, thus alleviating lung histopathological injury in NA. BATF was involved in mainly regulating naïve lymphocyte differentiation to T helper cell 17 (Th17) rather than regulatory T cells (Tregs). Our results demonstrate that BATF plays an important proinflammatory role in neutrophil asthma, and the inhibition of BATF could reduce lung inflammation by reducing IL-17A, acting as a potential therapeutic target.