Expansion of Interleukin‐22– and Granulocyte–Macrophage Colony‐Stimulating Factor–Expressing, but Not Interleukin‐17A–Expressing, Group 3 Innate Lymphoid Cells in the Inflamed Joints of Patients With Spondyloarthritis

Autor: Sijia Chen, Leonike J. J. van Mens, S. Menegatti, Hergen Spits, Dominique Baeten, Lars Rogge, Talia E. Latuhihin, Hulda S. Hreggvidsdottir, Iris C Blijdorp, Troy Noordenbos, Nataliya Yeremenko, Marleen G H van de Sande, Jochem H. Bernink
Přispěvatelé: AII - Inflammatory diseases, Clinical Immunology and Rheumatology, Graduate School, 01 Internal and external specialisms, Experimental Immunology, AGEM - Digestive immunity, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Institut Pasteur [Paris] (IP), AIMM Therapeutics [Amsterdam, the Netherlands], UCB Pharma [Slough], UCB Pharma [Brussels], Netherlands Scientific Organization (NWO Vici grant)/International, ERC_/European Research Council/International, Institut Pasteur [Paris], UCB Pharma Slough
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
MESH: Interleukin-17
[SDV]Life Sciences [q-bio]
medicine.medical_treatment
Arthritis
Rheumatoid
Interleukin 22
0302 clinical medicine
Synovial Fluid
Immunology and Allergy
Medicine
Lymphocytes
MESH: Arthritis
Rheumatoid
MESH: Middle Aged
Interleukin-17
Innate lymphoid cell
Middle Aged
MESH: Granulocyte-Macrophage Colony-Stimulating Factor
MESH: Case-Control Studies
3. Good health
Granulocyte macrophage colony-stimulating factor
Cytokine
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Immunity
Innate
Original Article
Female
Interleukin 17
medicine.drug
Adult
MESH: Interleukins
MESH: Spondylarthritis
Immunology
Proinflammatory cytokine
03 medical and health sciences
Rheumatology
MESH: Synovial Fluid
Spondyloarthritis
Spondylarthritis
Humans
Synovial fluid
030203 arthritis & rheumatology
MESH: Humans
business.industry
Interleukins
Granulocyte-Macrophage Colony-Stimulating Factor
MESH: Adult
MESH: Male
Immunity
Innate
030104 developmental biology
Case-Control Studies
MESH: Lymphocytes
IL17A
business
MESH: Female
Zdroj: Arthritis & Rheumatology (Hoboken, N.j.)
Arthritis & rheumatology (Hoboken, N.J.), 71(3), 392-402. John Wiley and Sons Ltd
Arthritis & rheumatology
Arthritis & rheumatology, 2019, 71 (3), pp.392-402. ⟨10.1002/art.40736⟩
Arthritis & rheumatology, Wiley, 2019, 71 (3), pp.392-402. ⟨10.1002/art.40736⟩
ISSN: 2326-5205
2326-5191
DOI: 10.1002/art.40736
Popis: International audience; Objective: Clinical trials of the anti-interleukin-17A (anti-IL-17A) antibody secukinumab have demonstrated a crucial role of the cytokine IL-17A in the pathogenesis of spondyloarthritis (SpA); however, its cellular source in this condition remains a matter of controversy. Group 3 innate lymphoid cells (ILC3s) have been recently identified as potent producers of proinflammatory cytokines, including IL-17A and IL-22, in a number of different tissues. This study was undertaken to characterize the presence and composition of ILCs, and investigate whether these cells are an important source of IL-17A, in the synovial tissue (ST) of patients with SpA.Methods: Matched ST, synovial fluid, and peripheral blood (PB) samples were obtained from SpA patients with actively inflamed knee joints. ILC subsets were characterized by flow cytometry. Gene expression analysis at the single-cell level was performed directly ex vivo and after in vitro activation. An IL-17A enzyme-linked immunospot assay was used to detect IL-17A-secreting cells.Results: ILCs, and particularly NKp44+ ILC3s, were expanded in inflamed arthritic joints. Single-cell expression analysis demonstrated that ST ILCs were clearly distinguishable from ST T cells and from their PB counterparts. Expression of the Th17 signature transcripts RORC, AHR, and IL23R was detected in a large proportion of ST ILC3s. These cells were capable of inducing expression of IL22 and CSF2, but not IL17A, in response to in vitro restimulation.Conclusion: Our findings demonstrate that absolute and relative numbers of ILC3s are enriched in the synovial joints of patients with SpA. However, these cells are not a significant source of IL-17A in this disease.
Databáze: OpenAIRE
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