Redefining innate cell development at oral barriers

Immunological control at the gingiva, a key oral barrier, is poorly understood. This is an oversight as loss of gingiva immune homeostasis results in the development of periodontitis, the most prevalent chronic inflammatory condition of humans. Crucially, periodontitis is known to exacerbate many extra-oral diseases, including Alzheimer’s Disease, gastrointestinal cancer, COPD and rheumatoid arthritis. Thus, delineating immune mechanisms underpinning gingiva health would ensure development of better periodontitis therapies with implications for the treatment of other diseases. This program will redefine our understanding of how effective gingival immunity is enforced. We recently revealed an unappreciated mechanism by which gingiva innate cells develop, identifying haematopoietic stem and progenitor cells (HSPC) resident in healthy gingiva that locally generate neutrophils and monocytes. Providing insights into the gingival haematopoietic niche we will outline how gingiva-resident HSPC support barrier integrity and impact periodontitis pathology, detailing functional consequences for neutrophils and monocytes of generation within gingival tissue. Moreover, we will ascertain whether gingiva-generated innate cells mediate inflammatory consequences in extra-oral tissues, providing unprecedented mechanistic insight into how periodontitis potentiates distal pathologies. Combined, this program will develop new concepts in mucosal immunology, substantially advancing the field of oral immunology, and identify novel strategies for therapeutic manipulation in periodontitis.