| 摘要 |
The invention provides a novel mouse IL-17F/IL-17A, and further provides uses of such mouse IL-17F/IL-17A in the characterization of the IL-17F/IL-17 A heterodimer. The present invention is also related to polynucleotides and polypeptides of the IL-17F/IL-17A signaling pathway, and targeting of the IL -17F/IL-17A signaling pathway in methods of treating IL-17F/IL-17A- associat ed disorders. The invention thus provides methods of using isolated IL-17F/I L-17A heterodimer, e.g., in a mouse model of airway inflammation, and specif ic or selective IL-17F/IL-17A modulators (e.g., signaling agonists or signal ing antagonists (e.g., specific or selective antagonistic antibodies, specif ic or selective antagonistic small molecules, etc.)). The invention also pro vides methods of screening for compounds capable of modulating IL-17F/IL-17A biological activity, e.g., IL-17F/IL-17A signaling antagonists (e.g., using the mouse model of airway inflammation), as well as methods of identifying whether the IL-17F/IL-17A modulator is a specific IL-17F/IL-17A modulator. T he invention is also directed to novel methods for diagnosing, prognosing, m onitoring, preventing, and/or treating IL-17F/IL-17A-associated disorders, i ncluding, but not limited to, inflammatory disorders (e.g., arthritis (inclu ding rheumatoid arthritis), psoriasis, systemiclupus erythematosus, and mult iple sclerosis), respiratory diseases (e.g., airway inflammation, chronic ob structive pulmonary disease, cystic fibrosis, asthma, allergy), transplant r ejection (including solid organ transplant rejection), and inflammatory bowe l diseases or disorders (e.g., ulcerative colitis, Crohn's disease). The pre sent invention is further directed to novel therapeutics and therapeutic tar gets identified by methods of screening of the invention, and uses of such i dentified therapeutics in methods of treatment and prevention of IL- 17F/IL- 17A-associated disorders.
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