The role of neutrophils in the regulation of the adaptive immunity in pemphigoid diseases

Epidermolysis Bullosa Acquisita (EBA) is an autoimmune blistering disorder that presents significant clinical challenges due to its chronic nature and profound impact on patient quality of life. Neutrophils are pivotal in EBA pathogenesis, particularly at the dermal-epidermal junction. While the precise etiology of EBA remains elusive, neutrophils are recognized as a prerequisite for disease development, with their effector functions being instrumental in tissue damage.

Recent research has expanded our understanding of neutrophil functionality beyond their traditional antimicrobial roles. Emerging evidence suggests that neutrophils may play a significant role in adaptive immunity by modulating T and B cell responses. Their interactions with lymphocytes and antigen-presenting cells indicate a complex influence on the immune response, though the full extent of their involvement in adaptive immunity remains to be elucidated.

Our investigation aims to delineate the immunoregulatory functions of neutrophils, with a particular focus on their interactions with the complement system and the implications for adaptive immunity. Utilizing an active EBA mouse model, we will characterize neutrophil populations across various organs (skin, spleen, and bone marrow) at different stages of disease progression through advanced immunophenotyping techniques.

To map neutrophil migration patterns, we will employ the photo-convertible transgenic mouse line Kaede. Furthermore, transcriptome analysis will provide insights into neutrophil gene expression profiles during EBA onset. We will implement neutrophil depletion strategies and generate neutrophil-specific MHC-II deficient mice to further elucidate their role in adaptive immune responses. Additionally, we will investigate the involvement of anaphylatoxin receptors C5aR1/2 in neutrophil-mediated immune modulation.

This comprehensive approach aims to highlight the multifaceted impact of neutrophils in EBA pathogenesis, extending beyond their well-established role in tissue damage. Through this project, we seek to advance our understanding of neutrophil biology and its implications in autoimmune blistering disorders, paving the way for targeted and more effective treatment strategies.