Skin Damage Signals Mediate Allergic Sensitization to Spatially Unlinked Antigen
Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Wang, Andrew
Abstract
Our current understanding of immunity to pathogens suggests that spatial coupling of antigens with danger signals is a required feature for the formation of immune memory. Thus, all experimental immunization protocols introduce both experimental adjuvants and antigens into the same place. More recently, food allergy models have utilized skin damage in lieu of exogenous experimental adjuvants to induce memory towards antigens absorbed in the same damaged area. However, whether skin-derived danger signals need to be spatially coupled to antigens for the formation of immune memory is unknown and led us to investigate the extent to which we could separate them in anatomical space. We observed that multiple modes of skin inflammation were sufficient to induce a humoral response to antigens solely introduced via the gastrointestinal tract. Thus, in addition to “local priming” of antigen entering through damaged skin, there also exists another paradigm of “remote priming” where the antigen is not spatially linked to the site of initiation of the immunostimulatory signals at an organismal level. We find that a narrow subset of endocrine cytokines induced by skin damage were necessary and sufficient for “remote priming” of antigen at any portal of entry. We further identify a cytokine code for directing the profile of humoral outcomes targeted towards a spatially uncoupled antigen. Our findings have important implications for understanding the fundamental characteristics of the formation of humoral memory with wide implications in diseases such as food allergy and in vaccinology.
Recommended Citation
Waizman, Daniel Alexander, "Skin Damage Signals Mediate Allergic Sensitization to Spatially Unlinked Antigen" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1338.
https://elischolar.library.yale.edu/gsas_dissertations/1338
