B Cells Contribute to Heterogeneity of IL-17 Producing Cells in Rheumatoid Arthritis and Healthy Controls

Paul Martin Schlegel,Claudia A Müller,Ingeborg Steiert,Ina Kötter,Peter Rosenberger

doi:10.1371/journal.pone.0082580

Paul Martin Schlegel, Claudia A Müller + Show 3 more

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https://doi.org/10.1371/journal.pone.0082580

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Journal: PloS one	Publication Date: Dec 5, 2013
Citations: 101	License type: CC BY 3.0

Affiliation: University of Tübingen, Hospital de Cruces

Abstract

Secretion of the proinflammatory cytokine Interleukin-17A (IL-17A) is the hallmark of a unique lineage of CD4 T cells designated Th17 cells, which may play a crucial role in the pathogenesis of rheumatoid arthritis (RA) and many autoimmune diseases. Recently, IL-17-producing cells other than T cells have been described, including diverse innate immune cells. Here, we show that the cellular sources of IL-17A in RA include a significant number of non-T cells. Multicolour fluorescence analysis of IL-17-expressing peripheral blood mononuclear cells (PBMC) revealed larger proportions of IL-17+CD3- non-T cells in RA patients than in healthy controls (constitutive, 13.6% vs. 8.4%, and after stimulation with PMA/ionomycin 17.4% vs. 7.9% p < 0.001 in both cases). The source of IL-17 included CD3-CD56+ NK cells, CD3-CD14+ myeloid cells as well as the expected CD3+CD4+ Th17 cells and surprisingly a substantial number of CD3-CD19+ B cells. The presence of IL-17A-expressing B cells was confirmed by specific PCR of peripheral MACS-sorted CD19+ B cells, as well as by the analysis of different EBV-transformed B cell lines. Here we report for the first time that in addition to Th17 cells and different innate immune cells B cells also contribute to the IL-17A found in RA patients and healthy controls.

Highlights

Since its first description in 1993 [1], IL-17A has received much attention as an important proinflammatory cytokine with a critical role in immune defence against extracellular pathogens as well as in the pathogenesis of different autoimmune diseases
Most of the IL-17+ lymphocytes were present within the CD3+ T cell subset in both stimulated and unstimulated peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis (RA) patients and healthy controls (Figure 1B)
The present study shows that in RA patients IL-17 is derived from a substantial number of cells other than the Th17 subset which include NK cells, other innate immune cells and in particular B lymphocytes in peripheral blood

Summary

Introduction

Since its first description in 1993 [1], IL-17A ( referred to as IL-17) has received much attention as an important proinflammatory cytokine with a critical role in immune defence against extracellular pathogens as well as in the pathogenesis of different autoimmune diseases It was first isolated from a cytotoxic T cell hybridoma (CTLA8) and later recognized to belong to a cytokine family which includes five additional members IL-17B, IL-17C, IL-17D, IL-17E ( known as IL-25) and IL-17F. IL-17A and IL-17F share the highest sequence homology and signal through a heterodimeric IL-17 receptor complex which comprises the two subunits IL-17RA and IL-17RC [2] Members of this cytokine family, especially IL-17A, act in different arms of the adaptive immune response [3], as well as in the coordinated regulation of innate immunity against bacterial and fungal infections [4]. Most recently B cells in mice and humans have been shwon to produce IL-17 in response to infection with Trypanosoma cruzi [19]

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