Abstract
Ndfip1 is an adaptor for the E3 ubiquitin ligase Itch. Both Ndfip1- and Itch-deficient T cells are biased toward Th2 cytokine production. In this study, we demonstrate that lungs from Ndfip1(-/-) mice showed increased numbers of neutrophils and Th17 cells. This was not because Ndfip1(-/-) T cells are biased toward Th17 differentiation. In fact, fewer Ndfip1(-/-) T cells differentiated into Th17 cells in vitro due to high IL-4 production. Rather, Th17 differentiation was increased in Ndfip1(-/-) mice due to increased numbers of IL-6-producing eosinophils. IL-6 levels in mice that lacked both Ndfip1 and IL-4 were similar to wild-type controls, and these mice had fewer Th17 cells in their lungs. These results indicate that Th2 inflammation, such as that observed in Ndfip1(-/-) mice, can increase Th17 differentiation by recruiting IL-6-producing eosinophils into secondary lymphoid organs and tissues. This may explain why Th17 cells develop within an ongoing Th2 inflammatory response.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bronchoalveolar Lavage Fluid / cytology
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Bronchoalveolar Lavage Fluid / immunology
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Cell Differentiation
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Cell Movement / immunology
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Eosinophils / immunology
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Eosinophils / pathology
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Inflammation / immunology
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Inflammation / pathology
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Intercellular Signaling Peptides and Proteins
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Interleukin-4 / biosynthesis
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Interleukin-4 / immunology
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Interleukin-6 / biosynthesis
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Interleukin-6 / immunology
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Lung / immunology*
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Lung / pathology
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophils / immunology
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Neutrophils / pathology
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Signal Transduction
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Th1-Th2 Balance
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Th17 Cells / immunology*
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Th17 Cells / pathology
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Th2 Cells / immunology
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Th2 Cells / pathology
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / immunology*
Substances
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Carrier Proteins
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Intercellular Signaling Peptides and Proteins
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Interleukin-6
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Membrane Proteins
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Ndfip1 protein, mouse
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Interleukin-4
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Itch protein, mouse
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Ubiquitin-Protein Ligases