Research ResourceImmunology

A Genome-Wide siRNA Screen Reveals Positive and Negative Regulators of the NOD2 and NF-κB Signaling Pathways

Science Signaling  15 Jan 2013:
Vol. 6, Issue 258, pp. rs3
DOI: 10.1126/scisignal.2003305

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Screening for Inflammation

NOD2 is a cytoplasmic pattern recognition receptor that detects bacterial peptidoglycan fragments and stimulates antimicrobial and proinflammatory immune responses through activation of mitogen-activated protein kinases and the transcription factor NF-κB, respectively. Loss- and gain-of-function mutations in the gene encoding NOD2 are associated with inflammatory disorders, including Crohn’s disease. Warner et al. performed a small interfering RNA screen to look for positive and negative regulators of NOD2 signaling in HEK 293 cells and validated some of their candidates in murine macrophages. In addition to identifying previously implicated mediators of NOD2 signaling, the screen identified previously uncharacterized regulators of NOD2 that interacted with core components of the NF-κB pathway. Together, these data suggest potential candidates that may be associated with Crohn’s disease.