RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

Koen Venken (), Peggy Jacques, Céline Mortier, Mark E. Labadia, Tine Decruy, Julie Coudenys, Kathleen Hoyt, Anita L. Wayne, Robert Hughes, Michael Turner, Sofie Van Gassen, Liesbet Martens, Dustin Smith, Christian Harcken, Joseph Wahle, Chao-Ting Wang, Eveline Verheugen, Nadia Schryvers, Gaëlle Varkas, Heleen Cypers, Ruth Wittoek, Yves Piette, Lieve Gyselbrecht, Serge Van Calenbergh, Filip Van den Bosch, Yvan Saeys, Gerald Nabozny and Dirk Elewaut ()
Additional contact information
Koen Venken: Ghent University
Peggy Jacques: Ghent University
Céline Mortier: Ghent University
Mark E. Labadia: Research and Development Boehringer-Ingelheim
Tine Decruy: Ghent University
Julie Coudenys: Ghent University
Kathleen Hoyt: Research and Development Boehringer-Ingelheim
Anita L. Wayne: Research and Development Boehringer-Ingelheim
Robert Hughes: Research and Development Boehringer-Ingelheim
Michael Turner: Research and Development Boehringer-Ingelheim
Sofie Van Gassen: Ghent University
Liesbet Martens: Ghent University
Dustin Smith: Research and Development Boehringer-Ingelheim
Christian Harcken: Research and Development Boehringer-Ingelheim
Joseph Wahle: Research and Development Boehringer-Ingelheim
Chao-Ting Wang: Research and Development Boehringer-Ingelheim
Eveline Verheugen: Ghent University
Nadia Schryvers: Ghent University
Gaëlle Varkas: Ghent University
Heleen Cypers: Ghent University
Ruth Wittoek: Ghent University
Yves Piette: Ghent University
Lieve Gyselbrecht: ASZ Aalst
Serge Van Calenbergh: Ghent University
Filip Van den Bosch: Ghent University
Yvan Saeys: Ghent University
Gerald Nabozny: Research and Development Boehringer-Ingelheim
Dirk Elewaut: Ghent University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular RORγt+T-betloPLZF− iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt+ iNKT and γδ-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, our findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07911-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07911-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07911-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().