Résumé
Rationale. Pulmonary ILC2s have been recently identified as a source of IL-5 and IL-13 during allergic inflammation and helminth infection. Fate-mapping experiments in our lab revealed that the transcription factor PLZF is upregulated during ILC2 development. We hypothesized that the PLZF null mouse would have an impaired innate type 2 response. Methods. Type 2 pulmonary inflammation was induced by intranasal treatment of PLZF null mice and wild-type littermates with either the protease papain, the cytokine IL-25, or saline for 3 days, followed by bronchoalveolar lavage, cellular isolation, and cytokine assays. PLZF null-wild type mixed bone marrow chimeras were generated to determine if the defects in the type 2 response were cell-intrinsic. Nippostrongylus brasilensis infection was used as a physiologic type 2 inflammatory stimulus. Results. While ILC2s were present in PLZF null mice, pulmonary eosinophilia and type 2 cytokine levels were both significantly reduced in response to papain, IL-25, or Nippostrongylus infection. Mixed chimera experiments indicated that these defects were intrinsic to ILC2s: fewer PLZF-null-derived pulmonary ILC2s were reconstituted and they were less able to produce type 2 cytokines, while eosinophils from wild-type or PLZF null mice responded comparably. Conclusion. Mice lacking PLZF have a defective type 2 immune response in response to various stimuli, due to impaired ILC2 effector function.