Journal of Molecular Medicine

, Volume 96, Issue 8, pp 819–829 | Cite as

Expression of IL-17F is associated with non-pathogenic Th17 cells

  • Florian Wanke
  • Yilang Tang
  • Konrad Gronke
  • Sabrina Klebow
  • Sonja Moos
  • Judith Hauptmann
  • Arthi Shanmugavadivu
  • Tommy Regen
  • Ilgiz A. Mufazalov
  • Lauren A. Gabriel
  • Sonja Reißig
  • Andreas Diefenbach
  • Florian C. Kurschus
  • Ari Waisman
Original Article


IL-17A and IL-17F share the highest sequence homology of the IL-17 family and signal via the same IL-17RA/RC receptor heterodimer. To better explore the expression of these two cytokines, we used a double reporter mouse strain (IL-17DR mice), where IL-17A expressing cells are marked by enhanced green fluorescent protein (eGFP) while red fluorescence protein (RFP) reports the expression of IL-17F. In steady state, we found that Th17 and γδ T cells only expressed IL-17A, while IL-17F expression was restricted to CD8 T cells (Tc17) and innate lymphoid cells (ILC type 3) of the gut. In experimental autoimmune encephalomyelitis, the vast majority of CNS-infiltrating Th17 cells expressed IL-17A but not IL-17F. In contrast, anti-CD3-induced, TGF-β-driven Th17 cells in the gut expressed both of these IL-17 cytokines. In line with this, in vitro differentiation of Th17 cells in the presence of IL-1β led primarily to IL-17A expressing T cells, while TGF-β induced IL-17F co-expressing Th17 cells. Our results suggest that expression of IL-17F is associated with non-pathogenic T cells, pointing to a differential function of IL-17A versus IL-17F.

Key messages

  • Naïve mice: CD4+ T cells and γδ T cells express IL-17A, and Tc17 cells express IL-17F. Gut ILC3 show differential expression of IL17A and F.

  • Th17 differentiation with TGF-β1 induces IL-17A and F, whereas IL-1β induced cells expressing IL-17A.

  • Th17 cells in EAE in CNS express IL-17A only.

  • Gut Th17 cells induced by anti-CD3 express IL-17A and F together as skin γδ T cells of IMQ-treated mice.


IL-17F Th17 cells IL-17A EAE Reporter mice 



We thank Bettina Kalt, Petra Adams, and Michaela Blanfeld for excellent technical assistance. We acknowledge Steffanie Bürger and Ina Schäfer from the Institute for Molecular Biology in Mainz for excellent assistance with the flow cytometry. We thank Svenja Schüler for help with statistical data representation. We are grateful to Richard Flavell and Chen Dong to share with us the reporter mouse lines used in this study. This work was supported by the Deutsche Forschungsgemeinschaft SFB/TR-128 to F.C.K. and A.W. and by SFB/TR-156 to A.W., A.D., and F.C.K.

Compliance with ethical standards

All experiments with mice were carried out in accordance with the guidelines of the Central Animal Facility Institution of Mainz and in accordance with relevant laws and guidelines with permission by the state Rhineland-Palatinate (animal experimentation applications (TVA) nos. G13-1-099 and G12-1-057). The approval process contained an ethical committee meeting instated by the Landesuntersuchungsamt Rheinland-Pfalz.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Florian Wanke
    • 1
    • 2
  • Yilang Tang
    • 1
  • Konrad Gronke
    • 3
    • 4
  • Sabrina Klebow
    • 1
  • Sonja Moos
    • 1
  • Judith Hauptmann
    • 1
  • Arthi Shanmugavadivu
    • 1
  • Tommy Regen
    • 1
  • Ilgiz A. Mufazalov
    • 1
  • Lauren A. Gabriel
    • 1
  • Sonja Reißig
    • 1
  • Andreas Diefenbach
    • 3
    • 4
  • Florian C. Kurschus
    • 1
    • 5
  • Ari Waisman
    • 1
  1. 1.University Medical Center of the Johannes Gutenberg University MainzInstitute for Molecular MedicineMainzGermany
  2. 2.Immunology, Inflammation & Infectious Diseases (I3), Discovery and Translational AreaRoche Pharma Research & Early Development (pRED)BaselSwitzerland
  3. 3.Institute of Medical Microbiology and HygieneUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
  4. 4.Institute of MicrobiologyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  5. 5.Department of DermatologyHeidelberg University HospitalHeidelbergGermany

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