The E3 Ubiquitin Ligase Adaptor Ndfip1 Regulates Th17 Differentiation by Limiting the Production of Proinflammatory Cytokines
Year: 2012
Type: article
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.
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Neurtophil Homeostasis and Lung Sequestration, Defining mechanisms for how Ndfip1 regulates T cell-mediated allergic responses, G4123701716, Nedd4-family adaptors and their regulation of T cell function, CXC Chemokines and Regulation of Granulopoiesis, G6146104298, A novel ubiquitin-ligase complex that prevents skin inflammation, Chemokine Compartmentalization and Neutrophil Accumulation in the Lung, Immune System Development and Regulation
OpenAlex ID: W2162931993