Innate and adaptive Type 2 cytokines drive mucosal eosinophilia (58.2)

Abstract

Abstract Helminth infection, asthma, and allergy share classical hallmarks of Type 2 immunity, in which Type 2 helper T (Th2) cells coordinate antibody production, mucus secretion, and innate effector recruitment via IL-4, IL-5, and IL-13 in affected tissues. Identifying the cells and interactions that drive Type 2 immunity may lead to improved treatments of human diseases. IL-5 is the specific survival and maturation factor for eosinophils and is essential for eosinophilia. Although eosinophils are a key Type 2 effector cell, their precise physiologic role in immunity is controversial. We generated an IL-5 reporter mouse and crossed it to our previously published IL-13 reporter strain to study eosinophil recruitment and tissue maintenance. IL-5-producing cells were found in resting lung, small intestine, and adipose tissue. After helminth infection, lung, liver, and intestinal IL-5-producing cells increased in number and in fluorescence intensity, corresponding with local eosinophilia. Intriguingly, much of the IL-5 signal arose not from Th2 cells, but instead from an “innate lymphocyte” population lacking T cell, B cell, and natural killer markers. Expression of IL-5 and IL-13 was similar but not identical. Innate lymphocytes did not express IL-4, and their distribution in mucosal tissues and their cytokine pattern suggest they may help maintain barrier and/or metabolic homeostasis. Studies are ongoing to define the relationship of these cells to Th2 cells and eosinophils.