Sterile triggers drive joint inflammation in TNF and IL-1beta dependent mouse arthritis models

Abstract

Arthritis is the most common extra-intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed the gut-joint-axis. The clinical association between gut and joint inflammation is further supported by the success of common therapeutic strategies and microbiota dysbiosis in both conditions. Most data however support a correlative relationship between gut & joint inflammation, while causative evidence is lacking. Using two independent transgenic mouse arthritis models, either TNF or IL1{beta} dependent, we demonstrate that arthritis develops independently of the microbiota and intestinal inflammation, since both lines develop full-blown articular inflammation under germ-free conditions. In contrast, TNF-driven gut inflammation is fully rescued in germ-free conditions indicating that the microbiota is driving TNF-induced gut inflammation. Together, our study demonstrates that, although common inflammatory pathways may drive both gut and joint inflammation, the molecular triggers initiating such pathways are distinct in these tissues.