Jenny Mannion, PhD

Allergic asthma is a chronic inflammatory airway disorder which is driven by T helper type 2 (Th2) cells, which respond to otherwise innocuous environmental allergens, such as house dust mite or pollen. Once CD4+ Th2 cells are established, they can remain in the lung tissue as resident memory cells (CD4+ Trm2 cells). Upon antigen re-exposure, CD4+ Trm2 cells are quickly reactivated to promote further inflammation. T regulatory cells (Tregs) play an indispensable role in limiting allergic inflammation. The expression of the chemokine receptor CCR4 has been implicated in the trafficking of Th2 cells into the lung tissue. However, CCR4 is also expressed on Tregs. Our understanding of the role of CCR4 in regulating versus promoting CD4+ Trm2 formation is limited given a lack of tools to interrogate this system. We have identified a subset of antigen presenting cells (APCs) which are activated by Th2 cytokines and produce the CCR4 ligands during allergic inflammation. We have developed a novel model in which we can delete CCR4 in an inducible and cell-specific manner. Our data indicates that CCR4 is required for Tregs to carry out their suppressive function during acute allergic inflammation. In this proposal, we will use models of allergic inflammation to investigate the role for CCR4 in dictating CD4+ Trm2 formation. Understanding how the formation of CD4+ Trm2 cells is regulated during allergic inflammation will represent an important step in establishing new approaches to treating allergic asthma.