6533b857fe1ef96bd12b4ea8
RESEARCH PRODUCT
IL-17 controls central nervous system autoimmunity through the intestinal microbiome
Ana AmorimImmo PrinzAlexandra GrillJula HuppertPhilippe Schmitt-kopplinTobias BoppAri WaismanSandrine IsaacTill StrowigMichael WittingMarco PrinzArthi ShanmugavadivuIlgiz A. MufazalovNir YogevJudith HauptmannMichaela BlanfeldMatthias KleinFlorian WankeChristoph ReinhardtRoman SankowskiAlexei NikolaevEric J. C. GálvezNicolás Gonzalo NúñezBurkhard BecherCarles UbedaTommy Regensubject
0301 basic medicineCentral Nervous SystemMaleEncephalomyelitis Autoimmune ExperimentalMultiple SclerosisreceptorImmunologyCentral nervous system610 Medicine & healthGut flora10263 Institute of Experimental Immunologymedicine.disease_causeAutoimmunityinterleukin-1703 medical and health sciencesMice0302 clinical medicinemedicinecytokineAnimalsHumanscnst-cellsMice Knockout2403 Immunologybiologygut microbiotaMultiple sclerosisExperimental autoimmune encephalomyelitisGeneral MedicineFecal Microbiota Transplantationneutralizationmedicine.diseasebiology.organism_classificationAdoptive Transfer3. Good healthGut EpitheliumGastrointestinal Microbiome030104 developmental biologyNeuroimmunologymedicine.anatomical_structureImmunology2723 Immunology and Allergy570 Life sciences; biologyTh17 CellssequencesFemaleInterleukin 17030217 neurology & neurosurgerydescription
Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in T-H cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-01 |