Regulation of inflammatory responses by IL-17F

By Xuexian O. Yang, S. Chang, Heon Park, R. Nurieva, Bhavin Shah, L. Acero, Yi-hong Wang, K. Schluns, R. Broaddus, Zhou Zhu and 1 more. Journal of Experimental Medicine, 2008

812 citations recorded by the source corpus.

Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/096bf03b868a100eecaf32c6b3cbdd8751c59a45

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Jetten
2. C. Dong
3. TA Wynn
4. V. Kuchroo
5. Yeonseok Chung
6. Xuexian O. Yang
7. M. Wilson
8. T. Korn

In Pathology and Forensic Medicine

1. TA Wynn
2. T. Korn
3. F. Powrie
4. C. Dong
5. E. Bettelli
6. M. Oukka
7. V. Kuchroo

Citations in the corpus

• Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. (2008, methodology): “2000) mice (the latter is deficient in all RORg isoforms including RORgt) and from Rorasg/sg and Rorasg/sgRorc / mice (Yang et al., 2008b) and their appropriate controls were stimulated with plate-bound anti-CD3 and anti-CD28 in the presence of various cytokines, and Foxp3 and IL-17 expression were…”
• Generation of follicular helper T cells is mediated by IL-21 but independent of TH1, TH2 or TH17 lineages (2008, methodology): “IL-17- and IL-17F-deficient mice were recently generated in our lab (Yang et al., 2008a).”
• IL-17 and Th17 Cells. (2009, background): “For example, Dong and colleagues (131) suggested that IL-17A but not IL-17F was required to induce EAE, whereas IL-17F but not IL-17A was required to induce airway neutrophilia upon allergen stimulation and severe immunopathology in the dextran sulfate sodium (DSS)-induced colitis model.”
• Bleomycin and IL-1β–mediated pulmonary fibrosis is IL-17A dependent (2010, background): “Functionally, IL­17F and IL­17A also appear to have opposing roles in the allergic lung, with IL­17F negatively regulating and IL­17A positively regulating Th2­ mediated inflammation (Yang et al., 2008).”
• A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease (2019, background): “IL-17F-deficiency improves the development of DSS-induced murine colitis, whereas IL-17-deficiency exaggerates the development of DSS-induced murine colitis, indicating that IL-17F rather than IL-17A is important in sustaining DSS colitis [171].”
• Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism (2009, background): “Similar experiments with Rag1-/- mice reconstituted with cells from mice deficient in both RORα and RORγ showed a complete resistance to EAE.”
• The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF (2011, neutral): “, whereas TNF, IL-21, IL-22 and IL-17F are not required for the development of EA”
• Intestinal homeostasis and its breakdown in inflammatory bowel disease (2011, background): “In acute DSS colitis, IL-17A has a protective role, whereas IL-17F seems to exacerbate diseas”
• A protective function for interleukin 17A in T cell–mediated intestinal inflammation (2009, neutral): “Those findings were subsequently supported by studies done elsewher”