Beware of wolves in sheep's clothing: immune cell plasticity and instability in health and disease

We read with great interest the article by Watad et al that characterised for the first time T lymphocytes in normal human enthesis.1 The authors demonstrated that entheseal resident CD4+ and CD8+ T cells show increased expression of immunomodulatory genes, including interleukin (IL)-10 and transforming growth factor-β compared with the circulating counterpart and that on stimulation they acquire the capability to produce tumour necrosis factor (TNF)-α and IL-17. Of note, normal entheseal T cells do not express FoxP3 as peripheral blood regulatory T cells (Treg), but its expression can be induced in specific conditions (eg, in the presence of phosphodiesterase type 4 inhibitor).\n\nThe plasticity and instability of immune cells in response to the stimuli of the local microenvironment are a highly interesting field of research under investigation in rheumatic and musculoskeletal diseases (RMDs).2 The article by Watad et al provides important insights that will help to better understand pathogenic mechanisms underlying the spectrum of spondyloarthritis (SpA). However, in light of data from experimental models and patients with RMDs, including SpA, some aspects should …