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.

Netherton综合征（NS）是一种严重的鱼鳞病，由失活的编码丝氨酸蛋白酶抑制剂LEKTI的SPINK5基因突变引起。Spink5 ^-/-小鼠概括了NS并由于表皮屏障的严重缺陷而因大量脱水而死于围产期。我们发现，删除的KLK5在SPINK5 ^{- / -}抢救新生儿的杀伤力（的Furio等人，2015年）。但是，Spink5 ^-/- Klk5 ^-/-小鼠在出生后第一周出现皮肤脱落和发炎，并且大多数（70％）死于P7。其余小鼠寿命短（即平均生存期为5个月），表明存在其他炎症途径。由于Cathelicidin在Spink5 ^-/-表皮中增加，因此我们研究了它是否可能与NS病理有关。的消融营在SPINK5 ^{- / -}抑制表皮炎症和异常恢复表皮分化，不过，它不能抑制overdesquamation和SPINK5 ^{- / -}营^{- / -}屈服于围产期由于皮肤屏障缺陷，类似于SPINK5 ^{- / -} 。Klk5和Camp的联合无效显着延长了Spink5 ^-/- Klk5的生存期^-/- Camp ^-/-小鼠。我们提供的证据表明，cathelicidin与体内与NS相关的皮肤炎症有关。因此，可以降低已知的cathelicidin表达的市售产品可重新用于NS的管理。