Abstract
Abstract Mice homozygous for the Tyr208Asn amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6spin mice) spontaneously develop a severe inflammatory disease resembling neutrophilic dermatoses in humans. Disease in Ptpn6spin mice is characterized by persistent footpad swelling and suppurative inflammation. This IL-1α dependent inflammation is mediated through SYK-RIPK1-TAK1-ASK1 kinases in Ptpn6spin mice independent of inflammasome activation. In the current study we have identified previously unknown role for CARD9 signaling as a critical regulator for Ptpn6spin-mediated footpad inflammation. Genetic deletion of CARD9 significantly rescued thePtpn6spin-mediated footpad inflammation. Mechanistically, enhanced IL-1α mediated signaling in Ptpn6spin mice neutrophils was dampened in Ptpn6spinCard9−/−mice. Collectively, this study identifies SHP-1 and CARD9 crosstalk as a novel regulator of IL-1α driven inflammation and opens future avenues for finding novel drug targets to treat neutrophilic dermatosis in humans.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
