R01AI153124

Humoral Immunoregulation of Allergic Disease by Follicular T Cell Subsets - 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.

Brigham & Womens Hospital

<P>THE GOALS ARE:</P><UL><LI>TO FOSTER FUNDAMENTAL CREATIVE DISCOVERIES, INNOVATIVE RESEARCH STRATEGIES, AND THEIR APPLICATIONS AS A BASIS FOR ULTIMATELY PROTECTING AND IMPROVING HEALTH;</LI><LI>TO DEVELOP, MAINTAIN, AND RENEW SCIENTIFIC HUMAN AND PHYSICAL RESOURCES THAT WILL ENSURE THE NATION'S CAPABILITY TO PREVENT DISEASE;</LI><LI>TO EXPAND THE KNOWLEDGE BASE IN MEDICAL AND ASSOCIATED SCIENCES IN ORDER TO ENHANCE THE NATION'S ECONOMIC WELL-BEING AND ENSURE A CONTINUED HIGH RETURN ON THE PUBLIC INVESTMENT IN RESEARCH; AND</LI><LI>TO EXEMPLIFY AND PROMOTE THE HIGHEST LEVEL OF SCIENTIFIC INTEGRITY, PUBLIC ACCOUNTABILITY, AND SOCIAL RESPONSIBILITY IN THE CONDUCT OF SCIENCE.</LI></UL><P>IN REALIZING THESE GOALS, THE NIH PROVIDES LEADERSHIP AND DIRECTION TO PROGRAMS DESIGNED TO IMPROVE THE HEALTH OF THE NATION BY CONDUCTING AND SUPPORTING RESEARCH:</P><UL><LI>IN THE CAUSES, DIAGNOSIS, PREVENTION, AND CURE OF HUMAN DISEASES;</LI><LI>IN THE PROCESSES OF HUMAN GROWTH AND DEVELOPMENT;</LI><LI>IN THE BIOLOGICAL EFFECTS OF ENVIRONMENTAL CONTAMINANTS;</LI><LI>IN THE UNDERSTANDING OF MENTAL, ADDICTIVE AND PHYSICAL DISORDERS; AND</LI><LI>IN DIRECTING PROGRAMS FOR THE COLLECTION, DISSEMINATION, AND EXCHANGE OF INFORMATION IN MEDICINE AND HEALTH, INCLUDING THE DEVELOPMENT AND SUPPORT OF MEDICAL LIBRARIES AND THE TRAINING OF MEDICAL LIBRARIANS AND OTHER HEALTH INFORMATION SPECIALISTS.</LI></UL>

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Boston, Massachusetts 021156110 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-25-301)

Amendment Since initial award the End Date has been extended from 02/28/26 to 02/28/31 and the total obligations have increased 519% from $509,137 to $3,150,648.