Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic... Show moreTh17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-gamma in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells. Show less
The worldwide resurgence of whooping cough (pertussis), even in highly vaccinated populations, demands improved pertussis vaccines. In this thesis a systems vaccinology approach is applied to... Show moreThe worldwide resurgence of whooping cough (pertussis), even in highly vaccinated populations, demands improved pertussis vaccines. In this thesis a systems vaccinology approach is applied to deepen knowledge of the immune responses evoked by different pertussis vaccines and compare this with a Bordetella pertussis infection since the latter induces robust protection. Infection-induced responses in mice conferred sterilizing protection that is caused by systemic immunity but more importantly by mucosal IgA, T-helper (Th)1/Th17 responses, and ‘trained’ innate immune cells in the lungs. An experimental outer membrane vesicle vaccine (omvPV) was compared with the two licensed vaccines, acellular vaccine (aPV), whole-cell vaccine (wPV) as well as a B. pertussis infection. OmvPV evoked a different immunoproteomic profile with respect to antibody levels, antigen specificity, and subclass distribution. Furthermore, omvPV confers equal protection in mice as wPV, but with a lower inflammatory response. In this thesis it is also shown that the immunization route is critical. Although subcutaneous omvPV immunization is effective, pulmonary administration lead to superior protection, comparable to infection-induced immunity and included hallmarks of protection such as pulmonary Th17 cells and mucosal IgA. The molecular and cellular signatures described in this thesis may have an important contribution to enhanced pertussis immunity. Show less
