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Open Access 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., http://arthritis-research.com/content/16/2/R62 and related letter by Dolff et al., http://arthritis-research.com/content/16/3/409

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/16/3/410


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 (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Letter

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.

Abbreviations

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.

References

  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