Session Title: Innate Immunity and Rheumatic Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Innate lymphoid cells (ILCs) represent a novel family of effector and regulatory cells in innate immunity and tissue remodelling. The family comprises several phenotypically and functionally distinct subsets that respond rapidly upon stimulation by producing various T helper cell cytokines such as IL-22, IL-17, IFNγ, TNF, IL-13 and IL-5, of which many are shown to be important in arthritis pathogenesis. The IL-17 and IL-22 producing ILCs are of major interest as they are implicated in chronic gut inflammation. Based on the broad clinical overlap between inflammatory bowel disease and spondyloarthritis (SpA) and the clinical importance of IL-17 in SpA we hypothesize that IL-17 and IL-22 producing ILCs contribute to inflammation and remodelling in SpA synovitis. As these cells have never been described in the joint we aimed at characterising ILC in chronic inflammatory arthritis.
Methods: ILCs (lineage negative, CD45+CD127+) were analysed and sorted by flow cytometry from synovial tissue and fluid from rheumatoid arthritis (RA) and SpA patients as well as in blood from SpA patients and healthy donors. mRNA expression of sorted and expanded cells was analysed by qPCR.
Results: ILCs were identified in blood as well as in synovial tissue and fluid from both RA and SpA patients. The frequency of ILCs was higher in the inflamed joint (0,5-3,3% of the lymphocyte population) than in the peripheral blood compartment (0,1%). In the inflamed joint, the ILC3 (CRTH2–NKp44+ckit+) and ILC1 (CRTH2–NKp44–ckit–) populations, shown to express IL-22 and IFNγ respectively in other tissues, were present in all samples whereas the Th2 cytokine expressing ILC2s (CRTH2+) were found in low frequencies. Frequencies of ILC subpopulations varied considerably between patients and no differences could be detected between RA and SpA patients. qPCR analysis of expanded cells from the synovium revealed that ILC1s expressed TBX21 whereas ILC3s expressed RORC. Accordingly, stimulated ILC3s expressed transcripts for both IL-23R and IL-22 but not IL-17. A trend towards higher frequency of total ILC and ILC3s was found in the blood of SpA patients compared to controls.
Conclusion: ILC1s and ILC3s are present in the chronically inflamed joint, are enriched compared to peripheral blood and express the key transcription factors associated with specific cytokine profiles. These data indicate that ILCs could contribute to local cytokine-driven immune alterations in SpA and RA.
H. S. Hreggvidsdottir,
M. C. Turina,
D. L. Baeten,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/phenotypic-and-molecular-profile-of-innate-lymphoid-cells-in-chronic-synovial-inflammation/