IL-33-responsive lineage -CD25 +CD44 hi lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs

Kathleen R. Bartemes, Koji Iijima, Takao Kobayashi, Gail M. Kephart, Andrew N. McKenzie, Hirohito Kita

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356 Scopus citations


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-7Ra (i.e., Lin -CD25 +CD44 hi lymphoid cells), and require IL-7Ra 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 (i.e., 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.

Original languageEnglish (US)
Pages (from-to)1503-1513
Number of pages11
JournalJournal of Immunology
Issue number3
StatePublished - Feb 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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