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Ulrich, Benjamin J; Kharwadkar, Rakshin; Chu, Michelle; Pajulas, Abigail; Muralidharan, Charanya; Koh, Byunghee; Fu, Yongyao; Gao, Hongyu; Hayes, Tristan A; Zhou, Hong-Ming; Goplen, Nick P; Nelson, Andrew S; Liu, Yunlong; Linnemann, Amelia K; Turner, Matthew J; Licona-Limon, Paula; Flavell, Richard A; Sun, Jie; Kaplan, Mark H (2022)

ALLERGIC AIRWAY RECALL RESPONSES REQUIRE IL-9 FROM RESIDENT MEMORY CD4(+) T CELLS

Sci Immunol 7(69):
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Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a subpopulation of CD4 T cells that secreted IL-9 as an obligate effector cytokine. IL-9-secreting cells had a resident memory T cell phenotype, and blocking IL-9 during a recall challenge or deleting IL-9 from T cells significantly diminished airway inflammation and airway hyperreactivity. T cells secreted IL-9 in an allergen recall-specific manner, and secretion was amplified by IL-33. Using scRNA-seq and scATAC-seq, we defined the cellular identity of a distinct population of T cells with a proallergic cytokine pattern. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multicytokine-producing CD4 T cell population was required for an allergen recall response.