| First Author | Zingkou E | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 10 | Pages | 165831 |
| PubMed ID | 32442469 | Mgi Jnum | J:300922 |
| Mgi Id | MGI:6504134 | Doi | 10.1016/j.bbadis.2020.165831 |
| Citation | Zingkou E, et al. (2020) Cathelicidin represents a new target for manipulation of skin inflammation in Netherton syndrome. Biochim Biophys Acta Mol Basis Dis 1866(10):165831 |
| abstractText | Netherton syndrome (NS) is a severe ichthyosis caused by inactivating mutations in the SPINK5 gene encoding the serine protease inhibitor LEKTI. Spink5(-/-) mice recapitulate NS and die perinatally from extensive dehydration as a result of a severe defect of the epidermal barrier. We showed that deletion of Klk5 in Spink5(-/-) rescues neonatal lethality (Furio et al., 2015). However, Spink5(-/-)Klk5(-/-) mice developed skin shedding and inflammation during the first week from birth and the majority (70%) succumbed on P7. The remaining mice lived short (i.e. mean survival was 5 months) indicating alternative inflammatory pathways. Since cathelicidin is increased in Spink5(-/-) epidermis, we investigated whether it could be implicated in NS pathology. Ablation of Camp in Spink5(-/-) suppressed epidermal inflammation and restored abnormal epidermal differentiation, nevertheless, it failed to inhibit overdesquamation and Spink5(-/-)Camp(-/-) succumbed perinatally due to skin barrier defect, similarly to Spink5(-/-). Joint invalidation of Klk5 and Camp significantly extended survival of Spink5(-/-)Klk5(-/-)Camp(-/-) mice. We provide evidence that cathelicidin is implicated in NS-associated skin inflammation in vivo. Therefore, marketed products that are known to reduce cathelicidin expression could be repurposed for the management of NS. |
