T Helper 17 Cells and Interferon Type I: Partners In Crime In SLE?

Odilia B.J. Corneth¹, Zana Brkic², Cornelia G. van Helden-Meeuwsen³, Radboud J.E.M. Dolhain⁴, Naomi I. Maria³, Sandra M.J. Paulissen⁴, Nadine Davelaar⁵, Jan Piet van Hamburg⁵, Paul L. Van Daele³, Virgil A. Dalm², Martin van Hagen³, Marjan A. Versnel² and Erik Lubberts⁶, ¹Rheumatology and Immunology, Erasmus Medical Center, Rotterdam, Netherlands, ²Erasmus Medical Center, Immunology, Rotterdam, Netherlands, ³Immunology, Erasmus Medical Center, Rotterdam, Netherlands, ⁴Rheumatology, Erasmus Medical Center, Rotterdam, Netherlands, ⁵Immunology, Erasmus MC, University Medical Center, Rotterdam, Netherlands, ⁶Erasmus Medical Center, Rheumatology, Rotterdam, Netherlands

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Auto-immunity, cytokines and interferons, SLE, T cells

Session Information

Session Title: Systemic Lupus Erythematosus-Human Etiology and Pathogenesis: Genetics and Genomics

Session Type: Abstract Submissions (ACR)

Background/Purpose:

A hallmark of systemic autoimmune diseases, such as systemic lupus erythematotsus (SLE), is the increased expression of interferon (IFN) type I inducible genes, the so-called IFN type I signature. Recently, a novel T helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, and IL-22, has also been implicated in autoimmune diseases. We investigated a possible link between these two pro-inflammatory immune pathways in SLE.

Methods:

25 SLE patients and 15 healthy controls (HC) were included. SLE patients were divided into an IFN type I signature negative (n=9) and positive (n=16) group as assessed by mRNA expression of IFN type I inducible genes. Peripheral expression of Th17 cytokines IL-17A, IL-17F and IL-22 by CD4+CCR6+ memory T cells was measured by flow cytometry and compared between IFN type I signature positive and negative patients and HC.

Results:

Increased fraction of IL-17A and IL-17A/IL-17F double producing CCR6+ cells was found in IFN type I positive patients compared with IFN type I negative patients and HC. The expression of IL-17A and IL-17F within CCR6+ cells correlated significantly with IFN scores. In addition, we found a significant correlation between BAFF and IL-21 producing CCR6+ cells.

Conclusion:

Here we show for the first time a correlation between IFN type I activation and expression of the Th17 cytokines in SLE patients. These data give new insight into the pathogenesis of SLE with possible implications for treatment.

Disclosure:

O. B. J. Corneth,
None;

Z. Brkic,
None;

C. G. van Helden-Meeuwsen,
None;

R. J. E. M. Dolhain,
None;

N. I. Maria,
None;

S. M. J. Paulissen,
None;

N. Davelaar,
None;

J. P. van Hamburg,
None;

P. L. Van Daele,
None;

V. A. Dalm,
None;

M. van Hagen,
None;

M. A. Versnel,
None;

E. Lubberts,
None.

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