Immune deficiency vs. immune excess in inflammatory bowel diseases—STAT3 as a rheo‐STAT of intestinal homeostasis

摘要

Genome‐wideassociationstudieshaveprovidedmanygeneticalterations,conferringsusceptibilitytomultifactorialpolygenicdiseases,suchasinflammatoryboweldiseases.Yet,howspecificgeneticalterationsfunctionallyaffectintestinalinflammationoftenremainselusive.Itisnoteworthythatalargeoverlapofgenesinvolvedinimmunedeficiencieswiththoseconferringinflammatoryboweldiseaseriskhasbeennoted.Thishasprovidednewargumentsforthedebateonwhetherinflammatoryboweldiseasearisesfromeitheranexcessoradeficiencyintheimmunesystem.Inthisreview,wehighlightthefunctionaleffectofaninflammatoryboweldisease‐riskallele,whichcannotbededucedfromgenome‐wideassociationstudiesdataalone.Asexemplifiedbythetranscriptionfactorsignaltransducerandactivatoroftranscription3(STAT3),weshowthatasinglegenecanhaveaplethoraofeffectsinvariouscelltypesofthegut.Theseeffectsmayindividuallycontributetotherestorationofintestinalhomeostasisontheonehandorpavethewayforexcessiveimmunopathologyontheother,asaninflammatory“rheo‐STAT”...