Regen, Tommy ORCID: 0000-0002-7275-3330, Isaac, Sandrine ORCID: 0000-0001-8306-3901, Amorim, Ana, Nunez, Nicolas Gonzalo, Hauptmann, Judith, Shanmugavadivu, Arthi, Klein, Matthias, Sankowski, Roman ORCID: 0000-0001-9215-8021, Mufazalov, Ilgiz A., Yogev, Nir, Huppert, Jula, Wanke, Florian, Witting, Michael ORCID: 0000-0002-1462-4426, Grill, Alexandra, Galvez, Eric J. C., Nikolaev, Alexei, Blanfeld, Michaela, Prinz, Immo ORCID: 0000-0002-8789-9578, Schmitt-Kopplin, Philippe ORCID: 0000-0003-0824-2664, Strowig, Till, Reinhardt, Christoph, Prinz, Marco, Bopp, Tobias, Becher, Burkhard, Ubeda, Carles ORCID: 0000-0003-0560-4658 and Waisman, Ari (2021). IL-17 controls central nervous system autoimmunity through the intestinal microbiome. Sci. Immunol., 6 (56). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2470-9468

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Regen, TommyUNSPECIFIEDorcid.org/0000-0002-7275-3330UNSPECIFIED
Isaac, SandrineUNSPECIFIEDorcid.org/0000-0001-8306-3901UNSPECIFIED
Amorim, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nunez, Nicolas GonzaloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauptmann, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shanmugavadivu, ArthiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sankowski, RomanUNSPECIFIEDorcid.org/0000-0001-9215-8021UNSPECIFIED
Mufazalov, Ilgiz A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yogev, NirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huppert, JulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wanke, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witting, MichaelUNSPECIFIEDorcid.org/0000-0002-1462-4426UNSPECIFIED
Grill, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galvez, Eric J. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolaev, AlexeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanfeld, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, ImmoUNSPECIFIEDorcid.org/0000-0002-8789-9578UNSPECIFIED
Schmitt-Kopplin, PhilippeUNSPECIFIEDorcid.org/0000-0003-0824-2664UNSPECIFIED
Strowig, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bopp, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becher, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ubeda, CarlesUNSPECIFIEDorcid.org/0000-0003-0560-4658UNSPECIFIED
Waisman, AriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602693
DOI: 10.1126/sciimmunol.aaz6563
Journal or Publication Title: Sci. Immunol.
Volume: 6
Number: 56
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2470-9468
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GUT MICROBIOTA; T-CELLS; INTERLEUKIN-17; CNS; NEUTRALIZATION; SEQUENCES; CYTOKINE; RECEPTORMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60269

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