IL-17 has been implicated in autoimmune inflammatory diseases such as arthritis. It was proposed that gut microbiota, [SFB]-induced Th17 cells were mediating autoimmune arthritis. Experiments with K/BxN mouse, a human model of spontaneous autoimmune [rheumatoid] arthritis, provided the initial support for this hypothesis.
However, a new paper in Journal of Immunology, suggests that IL-17 may have nothing to do with arthritis in K/BxN mice.
For this study, the authors have generated K/BxN mice deficient for IL-17A. Surprisingly, IL-17 deficient K/BxN mice showed no difference in arthritis development compared to WT K/BxN mice.
Even though IL-17 deficient K/BxN mice had no Th17 cells, levels of anti-GPI IgG auto-antibodies were not affected by absence of IL-17.
Next, the authors showed that antibiotic treatment could inhibit arthritis development in K/BxN mice independent of IL-17 expression.
Interestingly, the authors found that K/BxN mice with CD4-specific deletion of Bcl6 [and lacking T follicular helper T cells, Tfh] were resistant for arthritis development, implying role of Tfh and auto-antibodies in arthritis pathology [independent of IL-17].
In summary, this study suggests that IL-17 may not be involved in development of autoimmune [rheumatoid] arthritis in all cases. Rather, it is gut microbiota and Tfh/Ab that play dominant "pathogenic" role in this autoimmune disease.