Date: Monday, October 22, 2018
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Recent mouse studies of SpA pathogenesis have suggested that γδT-cells accumulate at entheseal regions in an IL-23 overexpression model and that these cells are responsible for the majority of local IL-17A production. Moreover a specific subset of γδT-cells (Vγ6) has been implicated in murine enthesitis and bone regeneration. This study aimed to examine the local distribution of γδT-cell subsets in normal human enthesis and identify which are most likely to participate in IL-23/17 axis driven inflammation.
Human entheseal soft tissue (EST) and peri-entheseal bone (PEB) was harvested from normal spinous process in patients undergoing elective spinal orthopaedic procedures. Interspinous EST was dissected from PEB and enzymatically digested. Cell sorting was used to isolate γδT-cells expressing the Vδ1 or Vδ2 isoforms of the TCR receptor γδT-cells expressing other Vδ isoforms were also collected. Following isolation RNA was purified and analysed by TaqMan array. Healthy entheseal tissue and peripheral blood collected from patients with either PsA or AS was stimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin and intracellular IL-17A production was measured in T-cell subsets.
Healthy EST contained a similar proportion of γδ subsets, (37%Vδ1 and 57%Vδ2) as was observed in peripheral blood (28%Vδ1 and 63%Vδ2), PEB contained a higher proportion of the Vδ1 subset and a lower proportion of the Vδ2 subset (50% and 39% respectively). The Vδ2 subset expressed a high relative abundance of IL-23/17 pathway associated transcripts including IL-23R, RORC and CCR6 they also expressed high relative abundance of TGFb1 transcript, a cytokine associated with immunomodulation and tissue residency. Following PMA stimulation IL-17A was robustly detected in CD4+ T-cells and in γδT-cells was detected predominantly in the Vδ2 subset although some signal was also observed in Vδ1 cells.
The Vδ2 subset of γδT-cells are present in entheseal tissues, their transcriptional profile and functional characteristics are consistent with IL-23 responsive IL-17 producing cells and closely resemble enthesitis associated murine Vγ6 γδT-cells. This data suggests that in humans the Vδ2 subset of γδT-cells are most likely to participate in SpA pathogenesis.
To cite this abstract in AMA style:Cuthbert R, Fragkakis EM, Bridgewood C, Dunsmuir R, Watad A, Rao A, Khan A, Marzo-Ortega H, Newton D, McGonagle D. The Vδ2 Subset of Γδt-Cells Are Present at Healthy Human Enthesis and Have Transcriptional and Functional Characteristics Consistent with a Capacity for IL- 17A Production in Response to IL-23 [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/the-v%ce%b42-subset-of-%ce%b3%ce%b4t-cells-are-present-at-healthy-human-enthesis-and-have-transcriptional-and-functional-characteristics-consistent-with-a-capacity-for-il-17a-production-in-response-t/. Accessed May 10, 2021.
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