IL-33–responsive lineage− CD25+ CD44hi lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs

KR Bartemes, K Iijima, T Kobayashi… - The Journal of …, 2012 - journals.aai.org
KR Bartemes, K Iijima, T Kobayashi, GM Kephart, AN McKenzie, H Kita
The Journal of Immunology, 2012journals.aai.org
Innate immunity provides the first line of response to invading pathogens and a variety of
environmental insults. Recent studies identified novel subsets of innate lymphoid cells that
are capable of mediating immune responses in mucosal organs. In this paper, we describe a
subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway
exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (< 12 h) production of
IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the …
Abstract
Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (< 12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33–responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1. 2, ICOS, Sca-1, and IL-7Rα (ie, Lin− CD25+ CD44 hi lymphoid cells), and require IL-7Rα for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (ie, ST2), and the Lin− CD25+ CD44 hi lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma.
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