5.2.1. Th17 Cells (IL-17+ CD4+ T Cells)

In 2005, a novel population of CD4+ T cells that secretes IL-17, clearly distinguished from Th1 and Th2, was identified [65,66]. IL-17 was initially recognized as a product of Th17 cells, but IL-17 production from other immune cells was also demonstrated [55].

IL-23 was thought to regulate the differentiation from CD4+ naive T cells to Th17 cells. But three independent studies revealed that IL-6 and TGF-β required to induce IL-17 in naïve T cells do not express IL-23 receptors [67–69]. Activation of STAT3 by IL-6 and TGF-β induces the master regulator of Th-17 cells, the transcription factor retinoid-related orphan receptor-γ (RORC), which expresses IL-23 receptor on the surface of Th 17 cells and enables them to secrete IL-17 in response to IL-23 [35]. IL-23 has now been shown to contribute to the lineage maintenance and proliferation of Th17.

The increased presence of Th17 in SpA patients has been reported. The serum levels of Th17 were higher in the peripheral blood in AS and PsA patients than in healthy controls [70,71]. Furthermore, several studies demonstrated the increased existence of Th17 in the inflamed tissue. The increase of Th17 cells in the synovial fluid in patients with PsA and reactive SpA has been reported [63,72,73]. As well as in SpA, the increased number of Th17 cells has also been identified in the skin of Ps patients, suggesting the involvement of local inflammation induced by Th17-derived IL-17 [74]. Immunohistological analysis of the facet joint in AS patients also revealed a higher expression of IL-17+ T cells [75].

In terms of the contribution of Th17 in the disease activity, correlations between the number of Th17 cells and disease activity score (BASDAI score) in AS [61] and the correlation between the number of Th17 cells in synovial fluid and C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28 in PsA were reported [72].
