Metformin alleviates inflammatory responses in acute allergic asthma by inhibiting ILC2s function

Allergic asthma was a type 2 immunity-mediated airway inflammatory disorder, in which type 2 innate lymphoid cells (ILC2s) play a pivotal role in response to allergen sensitization eosinophil infiltration, mucus hypersecretion, and bronchial hyperresponsiveness were its hallmark features. Despite the widespread use of glucocorticoids in allergic asthma management, drugs targeting ILC2s remain underdeveloped. Recently, emerging evidences have suggested that metformin displays anti-inflammatory properties during the challenge phase of allergic asthma. In order to further investigate the role and cellular mechanisms of metformin in the sensitization phase of allergic asthma, this study employed IL-33 alone or ovalbumin combined with papain to induce acute allergic asthma models in mice. During the sensitization process, metformin was administered via intraperitoneal injection. Histopathological and flow cytometric analyses revealed that metformin significantly attenuated airway inflammation, as evidenced by alleviated pathological damage, reduced mucus hypersecretion, decreased eosinophil infiltration, and diminished levels of IL-5 and IL-13 in bronchoalveolar lavage fluid. Additionally, the number and proportion of pulmonary ILC2s were notably decreased in metformin-treated mice. Furthermore, pulmonary ILC2s in metformin-treated mice displayed compromised cytokine production, diminished proliferation, and augmented death. These results indicate that metformin effectively alleviates airway inflammation in acute allergic asthma and its protective role may be mediated through the suppression of ILC2s. This study not only elucidates mechanistically the previously uncharacterized role of metformin in preventing allergen sensitization through inhibiting ILC2s, but also suggests that translationally metformin emerges as a potential prophylactic candidate for preventing the transition from subclinical inflammation to overt allergic asthma.

Acute allergic asthma; Airway inflammation; ILC2s; Metformin.