The following is a summary of “Differential regulation of IL-17A and IL-17F via STAT5 contributes to psoriatic disease,” published in the SEPTEMBER 2023 issue of Allergy & Immunology by Cole, et al.
IL-17A is known to play a significant role in various immune-mediated inflammatory diseases. On the other hand, the role of its counterpart, IL-17F, which shares 50% sequence homology with IL-17A, needs to be clarified. Clinical observations suggested that simultaneous inhibition of both IL-17A and IL-17F is more effective in treating psoriatic disease than inhibiting IL-17A alone, which indicates a potential role for IL-17F in this context. For a study, researchers sought to understand how IL-17A and IL-17F are regulated in psoriatic disease.
The study used a combination of in vitro systems and patient skin tissue samples to investigate the chromosomal, transcriptional, and protein expression profiles of IL-17A+ and IL-17F+ TH17 cells. Innovative techniques, such as single-cell RNA sequencing and a novel cytokine-capture approach, were applied alongside conventional assays like chromatin immunoprecipitation sequencing and RNA sequencing.
The findings confirmed that IL-17F is elevated more than IL-17A in psoriatic disease. Moreover, it was discovered that the two isoforms are predominantly expressed in distinct cell populations. Both IL-17A and IL-17F exhibit a high level of plasticity, meaning their expression can change, and proinflammatory signals and anti-inflammatory drugs, like methylprednisolone influence this flexibility. The genes for these isoforms have a broad H3K4me3 region at the IL17A–F locus, and they respond differently to STAT5/IL-2 signaling. Additionally, higher IL17F expression was associated with increased cell proliferation.
The study revealed significant differences in regulating IL-17A and IL-17F in psoriatic disease, leading to distinct inflammatory cell populations. It suggested that neutralizing both IL-17A and IL-17F may be necessary to inhibit IL-17-driven pathology effectively.
Source: jacionline.org/article/S0091-6749(23)00664-4/fulltext