H.J. Wu et al., “Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells,” Immunity, 32:815-27, 2010. Free F1000 Evaluation
The trillions of microbes that reside in the human gut shape their host’s immune system—for better or for worse. In a mouse model of autoimmune arthritis, Diane Mathis from Harvard University and colleagues found that gut bacteria can provoke autoimmune disease in distant parts of the body—the joints.
When investigators raised transgenic mice (which develop the disease at 4 weeks of age) in germ-free conditions, the animals developed a milder version of the disease much later. Germ-free mice lack immune cells called T helper 17 cells (Th17), because these cells require the gut bacteria called segmented filamentous bacteria (SFB) to properly develop. When Mathis blocked IL-17—secreted by Th17 cells—in the normally raised mouse model, disease progression was also attenuated.
Mathis and colleagues showed that after SFB induced the accumulation of Th17 cells in the gut, the immune cells traveled to the spleen, where they helped activate antibody-producing B cells. Since the B cells in this mouse model produced self-attacking antibodies that initiated arthritis, the presence of IL-17 acted like a catalyst, quickening the disease. Though more work remains, "it is not hard to imagine the clinical relevance," write Rochelle Marie Hinman and Faculty Member John Cambier.
Mathis and her team are currently investigating how this bacterium drives the development of the Th17 cells.
F1000 evaluators: C. Fagundes and M. Teixeira (Univ Federal de Minas Gerais) • A. Ho and S. Gaffen (Univ Pittsburgh) • E.C. Snow (Univ Kentucky) • R.M. Hinman and J. Cambier (National Jewish Med and Res Ctr)