Translational research of the pathogenesis and therapeutic approach to bacterial infection-derived autoimmune sequalae.
Laryngeal streptococcal infections, also known as “strep throat”, often proceed the development or exacerbation of chronic autoimmune conditions, including psoriasis, rheumatic fever, glomerulonephritis, lupus, and CNS autoimmune diseases. Several immunosusceptibilities have been suggested to explain the link between streptococcal infection and the pathogenesis of post-streptococcal disorders, such as molecular mimicry; however, the underlying mechanisms remain largely unexplained for such a long known clinical observation.
Our primary interest is to investigate the previously underappreciated molecular pathways highlighting lipid mediated T cell responses through CD1c presentation. Others’ and our past CD1 work have established the involvement of these unconventional T cells in human host defence, immune tolerance, and the pathogenesis of inflammatory diseases. In addition, aberrant lipid metabolism and profiles have been one of the key signatures developed under acute and reoccurring bacterial infection; yet we still know relatively little of their contribution in augmenting immune responses and the manifestation of autoimmune and autoinflammatory disorders.
We aim to further investigate CD1c-restricted T-cell functionalities in activating or dampening the post-streptococcal autoimmune regulation. We focus our expertise on exploring new molecular targets, developing therapeutic molecules, and discovering novel lipid species involved in regulating homeostasis and microbial defence. Our work also has translational implication to achieve immune intervention and mediating the outcome of human systemic autoimmune diseases.
Matthew Bottomley - CAMS Oxford Institute
Pablo Cespedes-Donoso - CAMS Oxford Institute
Tao Dong - CAMS Oxford Institute
Hashem Koohy - MRC Weatherall Institute of Molecular Medicine
Adan Pinto-Fernandez - CAMS Oxford Institute
Sumana Sharma - MRC Weatherall Institute of Molecular Medicine