Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease‐relevant neutrophil phenotype?

[摘要] Insevere,neutrophilicasthma,neutrophilsarethoughttohaveanimportantroleinboththemaintenanceofthediseaseandduringexacerbations.Thesepatientsoftendisplayexcessive,mucosalairwayinflammationwithunresolvingneutrophilia.Becausethisvariantofasthmaispoorlycontrolledbyglucocorticoids,specificpharmacologictargetingofneutrophilsseemsaplausibletherapeuticapproach.However,mostattemptswiththisapproachhavefailedintheclinic.Weproposethatthiscouldbeattributed,inpart,toanincompleteunderstandingoftheemergingnewinsightsunderlyingneutrophilhomeostasisandlifespan,neutrophilreversetransmigration,neutrophilphenotypes,andneutrophiltransdifferentiationinhumanhealthanddisease.Ofclinicalrelevance,recenttranslationalstudieshavestartedtouncoverdistinctneutrophilsubsetsinhumans,namelymatureandhypersegmentedphenotypesthathavebimodalimmunomodulatoryfunctionsduringanacuteinflammatoryresponse.Inthisreview,wewillelaborateonsomeofthenovelinsightsinneutrophilbiologyandattempttotranslatethemintopotentialconsequencesforpharmacologicinterventionofsevereneutrophilicasthma.Wespeculatethatthedisease‐relevantneutrophilphenotypeshouldbetargetedselectivelywithoutcompromisingtheimmunomodulatoryfunctionsessentialforhomeostasisandpulmonaryimmunity.However,theidentityandexactfunctionalroleofdistinctneutrophilphenotypesininflammatorydiseasesofthehumanairwayremainelusive...

[学科分类] 生理学

[关键词] translational;phenotypic switching;hypersegmented;immunomodulatory;myeloid suppressor cells