? Th9 cells in immediate hypersensitivity T helper subsets regulate inflammatory diseases, including the development of allergic lung inflammation associated with asthma. The development of T helper subsets in controlled by a network of transcription factors that promote the expression of cytokines and other genes associated with the ability of a T helper cell to promote disease. This proposal focuses on the most recently identified subset of T helper cells, Th9 cells that differentiate in response to TGF? and IL-4. In our preliminary data we have identified a requirement for Th9 cells for mast cell accumulation and function in allergic airway inflammation. Interestingly, we have identified a role for Th9 cells in facilitating immediate hypersensitivity responses. In the two Aims in this proposal we address basic questions that are critical for understanding Th9-dependent mast cell activity. In the first aim we will define the requirement for Th9 cells in immediate hypersensitivity using allergen sensitization and passive transfer models of IgE-dependent mast cell function. In the second Aim we will determine how Th9 cells regulate mast cell accumulation and activation, and determine which aspect is required for Th9-dependent mast cell function. Together, these Aims will define new mechanisms involved in Th9-dependent acute allergen responses.
These Aims will elucidate new pathways in acute and chronic allergic responses and highlight potentially new pathways for intervention.

Public Health Relevance

One of the hallmarks of asthma and other allergic diseases is a fast response upon allergen exposure that can lead to reactions ranging from hives to anaphylaxis and death. We are studying the role of a type of T cell called Th9 cells that are required for this immediate response. These studies will develop a new understanding of the mechanisms of allergic disease and identify new targets for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI129241-03
Application #
9616837
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Davidson, Wendy F
Project Start
2017-01-01
Project End
2021-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Pediatrics
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Rauber, Simon; Luber, Markus; Weber, Stefanie et al. (2017) Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nat Med 23:938-944