Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells

• DOI: 10.1073/pnas.1412308111
• Publication Date: 2014-08-12T06:59:19Z
• Authors: Thomas B. Sundberg; Hwan Geun Choi; Joo-Hye Song; Caitlin N. Russell; Mahmud M. Hussain; Daniel B. Graham; Bernard Khor; John Gagnon; Daniel J. O’Connell; Kavitha Narayan; Vlado Dančík; Jose R. Perez; Hans-Christian Re...; Nathanael S. Gray; Stuart L. Schreiber; Ramnik J. Xavier; Alykhan F. Shamji
• Keywords: Bosutinib; Proinflammatory cytokine; CD11c; Zymosan

Significance IL-10 plays an essential role in maintaining gut immune homeostasis as evidenced by the link between genetic perturbation of this anti-inflammatory cytokine and inflammatory bowel disease (IBD). Here, we describe a small-molecule screen that identified inhibition salt-inducible kinases (SIKs) strategy to enhance production macrophages dendritic cells. Significantly, IL-10–potentiating effects SIK are associated with reduced secretion cytokines IL-1β, IL-6, IL-12, TNF-α, these coordinated observed cells relevant IBD including CD11c + CX 3 CR1 hi from murine tissue human macrophages. Collectively, results identify promising approach treat increasing levels.