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Abstract Number: 199

Human Type 1 and Ncr-Negative Type 3 Innate Lymphoid Cells Accumulate in the Inflamed Synovium in Spondyloarthritis

Nataliya Yeremenko1,2,3, Silvia Menegatti4, Troy Noordenbos1,2,3, Leonieke J.J. van Mens1,2, Iris C. Blijdorp1,2,3, Kristine Germar1,2,3, Jochem Bernink5, Lars Rogge4, Hergen Spits5 and Dominique Baeten1,2,3, 1Amsterdam Rheumatology and immunology Center, Amsterdam, Netherlands, 2Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, Netherlands, 3Laboratory of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands, 4Immunoregulation Unit, Institut Pasteur, Paris, France, 5Department of Cell Biology and Histology, Academic Medical Centre/University of Amsterdam, Amsterdam, Netherlands

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Sunday, November 8, 2015

Title: Innate Immunity and Rheumatic Disease Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:  Spondyloarthritis (SpA) is a major form of chronic inflammatory arthritis characterized by inflammation of axial and peripheral joints and by pathologic new bone formation leading to ankylosis. Consistent genetic, experimental, and clinical evidence indicates that IL-23/IL-17 immune axis plays a pivotal role in the pathophysiology SpA. It remains, however, unknown which IL-23 responsive cells are the major cellular source of IL-17 in SpA. Innate lymphoid cells (ILCs) are an emerging family of innate immune cells that produce various cytokines, including IL-17 and IL-22, and play critical roles in regulation of inflammation and tissue remodelling. In this study we investigated the presence and phenotype of ILCs in the peripheral blood and inflamed peripheral joints of patients with SpA.

Methods: Paired peripheral blood (PB), synovial fluid (SF) and synovial tissue (ST) were obtained from SpA patients with actively inflamed knee joints. ILCs (lineage negative, CD45+CD127+CD161+) were analysed by flow cytometry.

Results: ILCs were present in all three compartments of patients with SpA. Analysis of ST revealed a significantly increased frequency of total ILCs in the joint compared with PB ((median (IQR) 0.37 (0.12-1.12)% of the lymphocyte population in ST versus 0.06 (0.04-0.09) % of the lymphocyte population in PB, p=0.016). Deep immunophenotyping of ILC subsets showed a statistically significant increase in the frequency of ILC1 (CRTH2–NKp44–ckit–) in ST (37.8%; 74.43-20.47%) versus SF (7.27%; 0.6-25.1 %, p=0.008) and PB (3.45%; 1.45-9.25%, p=0.004). The second most prominent ILCs in the joint were NCR-negative ILC3 (CRTH2–NKp44–ckit+), composing 33.45% (9.54-50.64%) of the total ILCs. NCR-positive ILC3 (CRTH2–NKp44+ckit+) and ILC2 (CRTH2+) populations were present in synovium at lower frequencies. 

Conclusion:  We observed in the inflamed ST of patient with spondyloarthritis an absolute and relative enrichment of both ILC1 and NCR-negative ILC3 as compared to PB and SF. As studies in other tissues such as gut and tonsil revealed that these IL-23 responsive ILC subsets can be an important source of IL-17 and /or IL-22 (1, 2), we will investigate the cytokine production by these synovial ILCs.

References:

  1. Geremia et al. J Exp Med. 2011 208(6):1127-1133
  2. Bernink et al. Nature Immunology 14(3):221-229
Disclosure: N. Yeremenko, None; S. Menegatti, None; T. Noordenbos, None; L. J.J. van Mens, None; I. C. Blijdorp, None; K. Germar, None; J. Bernink, None; L. Rogge, None; H. Spits, the biotech company AIMM therapeutics, 1,the biotech company AIMM therapeutics, 9; D. Baeten, None.

To cite this abstract in AMA style:

Yeremenko N, Menegatti S, Noordenbos T, J.J. van Mens L, Blijdorp IC, Germar K, Bernink J, Rogge L, Spits H, Baeten D. Human Type 1 and Ncr-Negative Type 3 Innate Lymphoid Cells Accumulate in the Inflamed Synovium in Spondyloarthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/human-type-1-and-ncr-negative-type-3-innate-lymphoid-cells-accumulate-in-the-inflamed-synovium-in-spondyloarthritis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/human-type-1-and-ncr-negative-type-3-innate-lymphoid-cells-accumulate-in-the-inflamed-synovium-in-spondyloarthritis/