Identification and phenotyping of innate lymphoid cells present in the diseased joints of patients with spondyloarthritis, rheumatoid arthritis and psoriatic arthritis

Authors: Al-Mossawi, J De Wit, B Kendrick,R Gundle, P Bowness

Background and aims Innate lymphoid cells (ILCs) have been recently identified at a number of different tissues and are thought to be an important class of innate immune cells involved in the initiation of the inflammatory response during health and disease. It is not known whether these cells exist in the human joint. We set out to identify and characterise these cells in the joints of patients with inflammatory arthritis.
Methods Matched synovial fluid and peripheral blood mononuclear cells from patients with spondyloarthritis (SpA) and psoriatic arthritis (PsA) were isolated and phenotyped using flow cytometry. In addition, cells from explanted orthopaedic surgical tissue samples were obtained from patients with SpA, PsA and rheumatoid arthritis (RA) and cultured in media containing interleukin-2 and interleukin-7. Intracellular cytokine staining was performed and analysed by flow cytometry.
Results A population of lineage-negative (i.e. negative for CD3, CD5 CD8, CD11b, CD11c, CD14, CD19, CD20, CD34, TCR-γδ) CD45 positive, IL-7R positive cells was identified in the synovial fluid and tissue of diseased human joints. Further phenotyping showed these to be either C-KIT positive ILC3 cells or C-KIT negative ILC1 cells. CRTH2 positive ILC2 cells were not detected. Comparison of matched blood and synovial fluid cells showed ILC3 populations were enriched in the joint and expressed HLA-DR.

Discussion and conclusions: ILC populations (type 1 and type 3) are pre present in the synovial fluid and synovial tissue of inflamed SpA, PsA and RA joints. These cells are capable of rapid cytokine release and are potentially highly inflammatory. They may also play a role in antigen presentation through HLA-DR expression. Understanding the role of ILCs in health and disease is important for deciphering the processes taking part in early SpA pathogenesis.

By way of further explanation I've extracted a couple of paragraphs from the Wikipedia entry for Innate Lymphoid Cells (ILC's)

Innate lymphoid cells (ILCs) are a group of innate immune cells that belong to the lymphoid lineage but do not respond in an antigen-specific manner, as they lack a B or T cell receptor. This relatively newly described group of cells has different physiological functions, some of them analogous to helper T cells, while also including the cytotoxic NK cells. In accordance, they have an important role in protective immunity and the regulation of homeostasis and inflammation, so their dysregulation can lead to immune pathology such as allergy and autoimmune disease.
In the environment of the intestinal tract, ILC3's have a crucial role in mediating the balance between symbiotic microbiota and the intestinal immune system. In response to inflammatory signals from the dendridic cells and gut epithelium, they produce IL-22 which increase the production of antimicrobial peptides and defensins. ILC3s also assist in immune responses to extracellular bacteria by maintaining the homeostasis of epithelia. Therefore, when malfunction appears, these cells may participate in the development of inflammatory bowel diseases (IBD).
Dx Oct 2006 B27+ undifferentiated spondlyarthropathy (uSpA) with mild sebhorrhoeic dermatitis and mild Inflammatory Bowel Disease (IBD) controlled by NSD since 2007.