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Open Access Open Badges Letter

Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply

Zana Brkic1, Odilia BJ Corneth12, Marjan A Versnel1 and Erik Lubberts12*

Author Affiliations

1 Department of Immunology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands

2 Department of Rheumatology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands

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Arthritis Research & Therapy 2014, 16:410  doi:10.1186/ar4578

See related research by Brkic et al., and related letter by Dolff et al.,

The electronic version of this article is the complete one and can be found online at:

Published:12 June 2014

© 2014 Brkic et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


We would like to reply to the letter by Dolff and colleagues [1] regarding our article in a recent issue of Arthritis Research & Therapy[2]. We thank the authors for their interest in our work and the critical reading of our article. The aim of our study was to investigate a possible association between the IFN type I signature and memory T helper 17 (Th17) cells and their cytokines in systemic lupus erythematosus (SLE). Since CCR6 can be expressed by regulatory T (Treg) cells, we have excluded CD25high cells to discriminate between CD4+CD45RO+CCR6+CD25 (primary Th17 cells) and Treg cells. Concerning the observation on co-expression of IL-17A with IFN-γ, we would like to remark that IFN-γ is an IFN type II, and not an IFN type I, cytokine and does not bind to the IFN type I receptor. Detection of IFN type I activity is hampered by the difficulty to assess the different subtypes of this cytokine. Therefore, analysis of IFN type I-induced gene expression in RNA from peripheral blood cells, the so-called IFN type I signature, is used as a measure for IFN type I activity. Although we fully agree with the authors that the relationship between Th cells and IFN type I deserves further study, their remark on the ‘genetic’ signature is confusing and probably refers to the IFN type I-induced gene expression signature, which is detected at the RNA level.

The relationship between CD25+ Tregs and IFN type I is certainly of interest for further study as these Tregs are carrying the IFN type I receptor and thus respond to increased systemic IFN type I activity in SLE. Also, follow-up studies with a focus on adaptive and innate cells producing IL-17, including the relation with IL-21 and IL-22 and plasticity, will be of interest [3,4]. In our article, we presented data supporting a potential co-activity between IFN type I and CD4+memory CCR6+ Th17 cytokines. Further studies are needed to confirm this co-activity with a focus on revealing the mechanism of this dangerous link in SLE.


IFN: Interferon; IL: Interleukin; SLE: Systemic lupus erythematosus; Th17: T helper 17; Treg: Regulatory T.

Competing interests

The authors declare that they have no competing interests.


  1. Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’.

    Arthritis Res Ther 2014, 16:409. BioMed Central Full Text OpenURL

  2. Brkic Z, Corneth OB, van Helden-Meeuwsen CG, Dolhain RJ, Maria NI, Paulissen SM, Davelaar N, van Hamburg JP, van Daele PL, Dalm VA, van Hagen PM, Hazes JM, Versnel MA, Lubberts E: T helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

    Arthritis Res Ther 2014, 16:R62. PubMed Abstract | BioMed Central Full Text OpenURL

  3. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells.

    Nat Immunol 2007, 8:639-646. PubMed Abstract | Publisher Full Text OpenURL

  4. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B: Fate mapping of IL-17-producing T cells in inflammatory responses.

    Nat Immunol 2011, 12:255-263. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL