Interleukin-17D produced by alveolar epithelial type Ⅱcellsalleviates LPS-induced acute lunginjury viatheNrf2 pathway.

Abstract

Sepsis engendersan imbalance in the body's inflammatory response, withcytokines assuminga pivotalrole in its progression. A relatively recentadditiontothe interleukin-17 family, denominatedInterleukin-17D (IL-17D), is notablyabundantwithinpulmonary confines.Nevertheless,its implicationin sepsis remains somewhatenigmatic. Thisstudy endeavorsto scrutinizethe participationof IL-17Din sepsis-induced acute lung injury (ALI). The levelsof IL-17D in theserum and bronchoalveolar lavage fluid(BALF)of bothhealthy cohortsand septicpatientswere ascertainedthroughan ELISA protocol.Forthecreationofasepsis-induced ALI model, intraperitoneallipopolysaccharide(LPS)injections were administered tomale C57/BL6 mice. Subsequently, weexaminedthefluctuations and repercussions associated withIL-17D in sepsis-induced ALI,probingitsinterrelationwith nuclear factor erythroid 2-related factor 2(Nrf2), alveolar epithelial permeability,and heme oxygenase-1. IL-17D levelsexhibited significant reductionboth intheserum and BALF ofseptic patients. Similarobservations manifestedin micesubjectedtoLPS-induced acute lung injury (ALI).Intraperitoneal administration ofrecombinant Interleukin 17Dprotein(rIL-17D)promptedincreasedexpression of claudin18 and concomitant enhancement ofalveolar epithelial permeability, thus, culminating inimproved lung injury. Alveolar epithelial typeⅡ(ATⅡ) cells wereidentified as thesource ofIL-17D,regulated byNrf2. Furthermore, a deficiency in HO-1 yieldedelevatedIL-17Dlevels, albeit administrationofrIL-17D amelioratedthe exacerbated pulmonarydamage resultingfromHO-1 deficiency. Nrf2fosters IL-17Dproduction withinATⅡcells,thereby conferringa protectiverolein sepsis-induced ALI.