Brkic, Z. (Zana)

Corneth, O.B.J. (Odilia)

Lubberts, E.W. (Erik)

Versnel, M.A. (Marjan)

PubMed

Zana Brkic

Odilia BJ Corneth

Marjan A Versnel

Erik Lubberts

Crossref

Arthritis Research & Therapy

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

Erasmus University Digital Repository

Brkic et al. Arthritis Research & Therapy 2014, 16:410http://arthritis-research.com/content/16/3/410LETTERResponse to ‘T-helper 17 cell cytokines andinterferon type I: partners in crime in systemiclupus erythematosus?’ – Authors’ replyZana Brkic1, Odilia BJ Corneth1,2, Marjan A Versnel1† and Erik Lubberts1,2*†See related research by Brkic et al., http://arthritis-research.com/content/16/2/R62 andrelated letter by Dolff et al., http://arthritis-research.com/content/16/3/409We would like to reply to the letter by Dolff and colleagues[1] regarding our article in a recent issue of ArthritisResearch & Therapy [2]. We thank the authors for theirinterest in our work and the critical reading of our article.The aim of our study was to investigate a possible associ-ation between the IFN type I signature and memory Thelper 17 (Th17) cells and their cytokines in systemic lupuserythematosus (SLE). Since CCR6 can be expressed byregulatory T (Treg) cells, we have excluded CD25high cellsto discriminate between CD4+CD45RO+CCR6+CD25−(primary Th17 cells) and Treg cells. Concerning the obser-vation on co-expression of IL-17A with IFN-γ, we wouldlike to remark that IFN-γ is an IFN type II, and not an IFNtype I, cytokine and does not bind to the IFN type I recep-tor. Detection of IFN type I activity is hampered by thedifficulty to assess the different subtypes of this cytokine.Therefore, analysis of IFN type I-induced gene expressionin RNA from peripheral blood cells, the so-called IFN typeI signature, is used as a measure for IFN type I activity.Although we fully agree with the authors that the relation-ship between Th cells and IFN type I deserves furtherstudy, their remark on the ‘genetic’ signature is confusingand probably refers to the IFN type I-induced geneexpression signature, which is detected at the RNA level.The relationship between CD25+ Tregs and IFN type I iscertainly of interest for further study as these Tregs arecarrying the IFN type I receptor and thus respond to in-creased systemic IFN type I activity in SLE. Also, follow-upstudies with a focus on adaptive and innate cells producing* Correspondence: e.lubberts@erasmusmc.nl†Equal contributors1Department of Immunology, Erasmus MC, University Medical Center,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands2Department of Rheumatology, Erasmus MC, University Medical Center,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands© 2014 Brkic et al.; licensee BioMed Central LtCommons Attribution License (http://creativecreproduction in any medium, provided the orDedication waiver (http://creativecommons.orunless otherwise stated.IL-17, including the relation with IL-21 and IL-22 andplasticity, will be of interest [3, 4]. In our article, wepresented data supporting a potential co-activity betweenIFN type I and CD4+memory CCR6+ Th17 cytokines.Further studies are needed to confirm this co-activity witha focus on revealing the mechanism of this dangerous linkin SLE.AbbreviationsIFN: Interferon; IL: Interleukin; SLE: Systemic lupus erythematosus; Th17: T helper 17;Treg: Regulatory T.Competing interestsThe authors declare that they have no competing interests.Published: 12 June 2014References1. Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cellcytokines and interferon type I: partners in crime in systemic lupuserythematosus?’. Arthritis Res Ther 2014, 16:409.2. Brkic Z, Corneth OB, van Helden-Meeuwsen CG, Dolhain RJ, Maria NI,Paulissen SM, Davelaar N, van Hamburg JP, van Daele PL, Dalm VA, vanHagen PM, Hazes JM, Versnel MA, Lubberts E: T helper 17 cell cytokinesand interferon type I: partners in crime in systemic lupus erythematosus?Arthritis Res Ther 2014, 16:R62.3. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M,Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenicspecificity of human interleukin 17-producing T helper memory cells.Nat Immunol 2007, 8:639–646.4. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, WilhelmC, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B: Fatemapping of IL-17-producing T cells in inflammatory responses. NatImmunol 2011, 12:255–263.doi:10.1186/ar4578Cite this article as: Brkic et al.: Response to ‘T-helper 17 cell cytokines andinterferon type I: partners in crime in systemic lupus erythematosus?’ –Authors’ reply. Arthritis Research & Therapy 2014 16:410.d. This is an Open Access article distributed under the terms of the Creativeommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andiginal work is properly credited. The Creative Commons Public Domaing/publicdomain/zero/1.0/) applies to the data made available in this article,

Response to 'T-helper 17 cell cytokines and interferon type I: Partners in crime in systemic lupus erythematosus?' - Authors' reply

Brkic, Zana

Corneth, Odilia

Versnel, Marjan

Lubberts, Erik

EUR Research Repository

English

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

EUR Research Information PortalResponse to 'T-helper 17 cell cytokines and interferon type I: partners in crime insystemic lupus erythematosus?' - Authors' replyPublished in:Arthritis Research & TherapyPublication status and date:Published: 01/01/2014DOI (link to publisher):10.1186/ar4578Document VersionPublisher's PDF, also known as Version of recordCitation for the published version (APA):Brkic, Z., Corneth, O., Versnel, M., & Lubberts, E. (2014). Response to 'T-helper 17 cell cytokines and interferon type I:partners in crime in systemic lupus erythematosus?' - Authors' reply. Arthritis Research & Therapy, 16(3).https://doi.org/10.1186/ar4578Link to publication on the EUR Research Information PortalTerms and Conditions of UseExcept as permitted by the applicable copyright law, you may not reproduce or make this material available to any third partywithout the prior written permission from the copyright holder(s). Copyright law allows the following uses of this materialwithout prior permission:            • you may download, save and print a copy of this material for your personal use only;            • you may share the EUR portal link to this material.In case the material is published with an open access license (e.g. a Creative Commons (CC) license), other uses may beallowed. Please check the terms and conditions of the specific license.Take-down policyIf you believe that this material infringes your copyright and/or any other intellectual property rights, you may request itsremoval by contacting us at the following email address: openaccess.library@eur.nl. Please provide us with all the relevantinformation, including the reasons why you believe any of your rights have been infringed. In case of a legitimate complaint,we will make the material inaccessible and/or remove it from the website.LETTERResponse to ‘T-helper 17 cell cytokines andinterferon type I: partners in crime in systemiclupus erythematosus?’ – Authors’ replyZana Brkic1, Odilia BJ Corneth1,2, Marjan A Versnel1† and Erik Lubberts1,2*†See related research by Brkic et al., http://arthritis-research.com/content/16/2/R62 andrelated letter by Dolff et al., http://arthritis-research.com/content/16/3/409We would like to reply to the letter by Dolff and colleagues[1] regarding our article in a recent issue of ArthritisResearch & Therapy [2]. We thank the authors for theirinterest in our work and the critical reading of our article.The aim of our study was to investigate a possible associ-ation between the IFN type I signature and memory Thelper 17 (Th17) cells and their cytokines in systemic lupuserythematosus (SLE). Since CCR6 can be expressed byregulatory T (Treg) cells, we have excluded CD25high cellsto discriminate between CD4+CD45RO+CCR6+CD25−(primary Th17 cells) and Treg cells. Concerning the obser-vation on co-expression of IL-17A with IFN-γ, we wouldlike to remark that IFN-γ is an IFN type II, and not an IFNtype I, cytokine and does not bind to the IFN type I recep-tor. Detection of IFN type I activity is hampered by thedifficulty to assess the different subtypes of this cytokine.Therefore, analysis of IFN type I-induced gene expressionin RNA from peripheral blood cells, the so-called IFN typeI signature, is used as a measure for IFN type I activity.Although we fully agree with the authors that the relation-ship between Th cells and IFN type I deserves furtherstudy, their remark on the ‘genetic’ signature is confusingand probably refers to the IFN type I-induced geneexpression signature, which is detected at the RNA level.The relationship between CD25+ Tregs and IFN type I iscertainly of interest for further study as these Tregs arecarrying the IFN type I receptor and thus respond to in-creased systemic IFN type I activity in SLE. Also, follow-upstudies with a focus on adaptive and innate cells producingIL-17, including the relation with IL-21 and IL-22 andplasticity, will be of interest [3, 4]. In our article, wepresented data supporting a potential co-activity betweenIFN type I and CD4+memory CCR6+ Th17 cytokines.Further studies are needed to confirm this co-activity witha focus on revealing the mechanism of this dangerous linkin SLE.AbbreviationsIFN: Interferon; IL: Interleukin; SLE: Systemic lupus erythematosus; Th17: T helper 17;Treg: Regulatory T.Competing interestsThe authors declare that they have no competing interests.Published: 12 June 2014References1. Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cellcytokines and interferon type I: partners in crime in systemic lupuserythematosus?’. Arthritis Res Ther 2014, 16:409.2. Brkic Z, Corneth OB, van Helden-Meeuwsen CG, Dolhain RJ, Maria NI,Paulissen SM, Davelaar N, van Hamburg JP, van Daele PL, Dalm VA, vanHagen PM, Hazes JM, Versnel MA, Lubberts E: T helper 17 cell cytokinesand interferon type I: partners in crime in systemic lupus erythematosus?Arthritis Res Ther 2014, 16:R62.3. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M,Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenicspecificity of human interleukin 17-producing T helper memory cells.Nat Immunol 2007, 8:639–646.4. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, WilhelmC, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B: Fatemapping of IL-17-producing T cells in inflammatory responses. NatImmunol 2011, 12:255–263.doi:10.1186/ar4578Cite this article as: Brkic et al.: Response to ‘T-helper 17 cell cytokines andinterferon type I: partners in crime in systemic lupus erythematosus?’ –Authors’ reply. Arthritis Research & Therapy 2014 16:410.* Correspondence: e.lubberts@erasmusmc.nl†Equal contributors1Department of Immunology, Erasmus MC, University Medical Center,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands2Department of Rheumatology, Erasmus MC, University Medical Center,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands© 2014 Brkic et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.Brkic et al. Arthritis Research & Therapy 2014, 16:410http://arthritis-research.com/content/16/3/410

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