For mucosal vaccines to reach their full potential in disease prevention it is imperative that we understand the molecular mechanisms of IgA antibody secreting cell (ASC) homing to mucosal tissues. This is particularly important if vaccines are to be designed which are administered via one mucosal surface but where antibody protection is also desirable at other mucosal sites. We hypothesize that lymphocyte homing to mucosal tissues is a highly regulated process and that highly similar mucosal tissues exhibit distinct, functionally relevant, adhesion molecule phenotypes. We further hypothesize that it is possible to design vaccination protocols which result in robust antibody responses to select mucosal tissues. In this study we propose to define differences in the adhesion molecule phenotype of mucosal tissues. We then propose to use this knowledge to test the hypothesis that through the selective upregulation of the chemokine receptor CCR10, antigen specific IgA antibody secreting cells can be selectively targeted to relevant mucosal tissues.
Most pathogens enter the body through mucosal surfaces. The immune system is uniquely equipped to protect these surfaces through the production of IgA antibodies. We propose to study the mechanisms by which IgA antibody producing cells home to, and accumulate in, mucosal tissues. This knowledge will ultimately lead to the design of more effective mucosal vaccines
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