The invasion (left) of neutrophils (red) into arthritic joints is prevented (right) by a CpG.

Arthritis sufferers might get some therapeutic relief from bacterial nucleic acids that usually goad on inflammation, if results from Wu et al. (page 1911) are any indication. Some of these short CpG repeats (CpGs) are now shown to prevent arthritis progression in a mouse model.

CpGs are well-known proinflammatory molecules that activate dendritic cells (DCs) via toll-like receptor (TLR)-9. The DCs then stimulate T cells and B cells. CpGs are therefore used in the clinic to enhance protection against infections and tumor development. But immune enhancement can be harmful if the response is directed against the host's own antigens. CpGs and other TLR ligands, for example, further disease progression in many mouse arthritis models.

In some mouse models of allergy and asthma, however, CpGs exert a protective role. In these mice, CpG-activated DCs somehow jumpstart the proliferation of protective T cell subsets and stop B cells from secreting allergy-causing antibodies. Wu et al. wondered whether CpGs had a similar therapeutic effect on arthritis.

The team tested several known CpGs in mice that had developed arthritis in response to injected serum antibodies. Two structurally similar CpGs halted disease progression. Unlike disease-promoting CpGs, these helpful CpGs stimulated DCs to activate natural killer (NK) cells instead of T and B cells. The NK cells then produced interferon (IFN)-γ. This normally proinflammatory cytokine blocked neutrophil trafficking into the diseased joints, thereby lessening inflammation.

The authors attribute this disease-dampening effect to the fact that the T/B cell-mediated initiation phase had passed by the time the CpGs were delivered. The NK-mediated therapeutic effects may translate to human arthritis treatments, as T and B cells have usually already done their dirty work by the time patients arrive in the clinic.