Schematic diagram illustrating possible IL-17A–driven pathogenesis in frozen shoulder. The presence of IL-17A–secreting T cells results in the fibrosis, inflammation, and further recruitment of pathogenic T cells, resulting in disease chronicity, which can be attenuated by use of an anti–IL-17A monoclonal antibody.

New research by Institute of Infection, Immunity and Inflammation scientists may have provided a key step in translational medicine for frozen shoulder patients.

A common fibrotic disease characterised by the onset of pain and restricted range of shoulder movement with a significant socioeconomic impact, frozen shoulder affects up 10 per cent of people of working age.

Inflammation is known to play a crucial role in tissue fibrosis, and various cytokines have been implicated in driving the progression of many fibrotic diseases including liver, lung and kidney fibrosis.

This work, published in PNAS, has looked at human frozen shoulder tissue samples at a ‘single’ cell level and found that important immune cells (T cells) and cytokines (interleukin 17) are fundamental drivers of the disease.

Importantly, blocking this molecular interleukin 17 pathway limits key aspects of frozen shoulder and may be a therapeutic opportunity for this debilitating disease.

Co-author Neal Millar, Professor of Orthopaedic Surgery and Musculoskeletal Science in the Institute, said: "Frozen shoulder has a huge disease burden in society.

"Using cutting-edge technologies, we have dissected a key role for the immune system in the disease process while blocking IL-17A.

"This has been hugely successful in other musculoskeletal conditions and may provide a novel treatment for this debilitating disease as well as being applicable to other serious fibrotic diseases - of the lung or liver - that lack effective treatments."

Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis

  • Moeed Akbar, Lindsay A. N. Crowe, Michael McLean, Emma Garcia-Melchor, Lucy MacDonald, Kristyn Carter, Umberto G. Fazzi, David Martin, Angus Arthur, James H. Reilly, Iain McInnes, and Neal L. Millar
  • PNAS September 28, 2021 118 (39) e2102715118; https://doi.org/10.1073/pnas.2102715118

Funding: This study was supported by a Medical Research Council UK Award (MR/R020515/1 to N.L.M.).

Image legend: Figure 6 - Targeting IL-17A in frozen shoulder. Schematic diagram illustrating possible IL-17A–driven pathogenesis in frozen shoulder. The presence of IL-17A–secreting T cells results in the fibrosis, inflammation, and further recruitment of pathogenic T cells, resulting in disease chronicity, which can be attenuated by use of an anti–IL-17A monoclonal antibody.

First published: 27 September 2021

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