Humoral Immunoregulation of Allergic Disease by Follicular T Cell Subsets

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Pathogenic antibodies promote and exacerbate allergic inflammation. Antibody responses are controlled by a delicate balance between stimulatory signals from T follicular helper (Tfh) cells and inhibitory signals from T follicular regulatory (Tfr) cells. Alterations in this balance can lead to pathogenic antibody responses and disease. Although subsets of Tfh and Tfr cells have been implicated in controlling allergies, the precise mechanisms of how these cells regulate distinct stages of allergic inflammation are not currently known. We hypothesize that individual subsets of Tfh and Tfr cells have unique and multifaceted roles during distinct stages of allergic inflammation. Moreover, we hypothesize that the composition of Tfh and Tfr subsets evolves over time to orchestrate allergic disease. By elucidating how Tfh and Tfr cell subsets control allergic inflammation, new strategies can be developed that specifically target pathogenic responses during allergies without affecting broad immune responses. To test these hypotheses, we have developed a number of novel mouse models for the in-depth study of the roles of specialized subsets of Tfh and Tfr cells in allergies. Our aims are to 1) Determine how Tfr cells control allergic inflammation through regulating B, Tfh13 and Tfh21 cells; and 2) Assess how the evolving composition of unique Tfh cell subsets orchestrates allergic inflammation. Our goals are to elucidate mechanisms used by Tfh and Tfr cell subsets to regulate allergies, and to identify targeted strategies to limit allergic inflammation.