INTRODUCTION: A hallmark of systemic autoimmune diseases like systemic lupus 
erythematosus (SLE) is the increased expression of interferon (IFN) type I 
inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset 
(Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been 
implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to 
investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, 
and/or IL-22 are increased in SLE patients and whether this increase is related 
to the presence of IFN type I signature.
METHODS: In total, 25 SLE patients and 15 healthy controls (HCs) were included. 
SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and 
negative (IFN⁻) (n = 9) patients, as assessed by mRNA expression of 
IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, 
and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow 
cytometry and compared between IFN⁺, IFN⁻ patients and HCs.
RESULTS: Increased percentages of IL-17A and IL-17A/IL-17F double-producing 
CCR6⁺ cells were observed in IFN⁺ patients compared with IFN⁻ patients and HCs. 
IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with 
IFIG expression. In addition, we found significant correlation between B-cell 
activating factor of the tumor necrosis family (BAFF)-a factor strongly 
correlating with IFN type I - and IL-21 producing CCR6⁺ cells.
CONCLUSIONS: We show for the first time higher percentages of IL-17A and 
IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, 
supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE 
pathogenesis.