Pyroptosis in neutrophils in pemphigoid deseases

Vitamin D is an important immunomodulator and exerts a great influence in allergic diseases such as asthma. Lower vitamin D is typically associated with increased asthma severity and reduced glucocorticoid response. One important mechanism whereby vitamin D/VDR signaling is reported to control inflammation is by suppressing inflammasome activation and IL-1β release through different pathways. Importantly, the literature demonstrated that NLRP3 inflammasome activation and IL-1β release are implicated in the pathogenesis of neutrophilic asthma. Neutrophilic asthma is the most common asthma endotype among adults. Although it represents 5-10% of asthmatic patients, neutrophilic asthma contributes to the majority of asthma morbidity and associated healthcare costs with clear unmet need due to the severity of the disease and resistance to corticosteroids. Therefore, we hypothesized that vitamin D might inhibit inflammasome activation during neutrophilic lung inflammation. Our study aims to reveal a new therapeutic target for the use of vitamin D in the treatment of severe steroid resistant asthma.

For the COVID-19 project, a Cohort of SARS-CoV-2 patients with and without Vit D administration will be used to determine whether Vit D downregulates inflammasome activation in SARS-CoV-2 infected patients.

Our preliminary data showed that SARS-CoV-2 patients administered with Vit D showed a reduction in inflammasome activation markers. This promising data paved the way for the in vitro work where mimicking of viral infection in monocytes and macrophages with PolyI:C will be done followed by Vit D treatment to determine its effect on inflammasome activation and its mechanism of action in the context of SARS-CoV-2.