Innate Lymphoid Cells Are Present at Normal Human Enthesis Providing a Potential Mechanism for Spondyloarthropathy Pathogenesis

Richard Cuthbert¹, Evangelos M. Fragkakis¹, Peter Millner², Robert Dunsmuir², Yasser El-Sherbiny¹ and Dennis McGonagle¹, ¹Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ²Department of Spinal Surgery, National Health Service, Leeds, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: enthesis, inflammatory arthritis, innate immunity and spondylarthritis

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: The pathogenesis of murine spondyloarthropathy (SpA) has been intimately linked to the presence of IL-23 responsive, innate like lymphocytes at peripheral and spinal enthesis. Human SpAs are associated with SNPs in genes related to the IL-23 pathway and drugs that block IL-12/23 have shown efficacy. We hypothesised that the normal human enthesis has a population of resident innate lymphoid cells (ILCs) that could be key in governing entheseal immune homeostasis.

Methods: Normal spinal enthesis were harvested from patients undergoing spinal decompression surgery and enzymatically digested prior to sorting or flow cytometry. Cellular immunophenotyping and cell sorting was performed on enthesis samples harvested from 6 patients; ILC3s were identified as lineage (CD3- TCRγδ- TCRαβ- CD19- CD14- CD11c- CD1a- CD303- FcεRI- CD34- CD123-) and CRTH2 negative with positive expression of CD45, CD127, CRTH2, CD117. ILC2 were identified as lineage negative with positive expression of CD45, CD127 and CRTH2. The expression of RORγt transcript was tested in sorted populations by RTqPCR. Anterior cruciate ligament femoral enthesis was obtained from subjects with knee OA and injured enthesis undergoing repair were also collected and analysed by immunohistochemistry (IHC).

Results: All sorted samples contained ILC3s, median proportion 0.09% (range 0.015-0.63). Transcript analysis confirmed the expression of RORγt transcript in sorted ILC3 populations, with ILC3s expressing 51-fold greater relative expression in comparison to unsorted digests. 5 of 6 sorted samples contained ILC2s, median proportion 0.20% (range 0-0.49). RORγt expression was detected in knee OA and there was widespread expression of RORγt in inflammatory infiltrates in injured enthesis as shown by IHC.

Conclusion: Our findings show that ILCs are present in the normal human spinal enthesis and may be greatly increased in frequency following injury. These findings provide strong evidence of ILC presence in normal human enthesis and suggest a potential link between cellular dysregulation of the IL-23/17 axis and SpA pathology at sites of micro damage.

Disclosure: R. Cuthbert, None; E. M. Fragkakis, None; P. Millner, None; R. Dunsmuir, None; Y. El-Sherbiny, None; D. McGonagle, None.

To cite this abstract in AMA style:

Cuthbert R, Fragkakis EM, Millner P, Dunsmuir R, El-Sherbiny Y, McGonagle D. Innate Lymphoid Cells Are Present at Normal Human Enthesis Providing a Potential Mechanism for Spondyloarthropathy Pathogenesis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/innate-lymphoid-cells-are-present-at-normal-human-enthesis-providing-a-potential-mechanism-for-spondyloarthropathy-pathogenesis/. Accessed .

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