RESEARCH HIGHLIGHTS Nature Reviews Rheumatology 10, 638 (2014); published online 30 September 2014; doi:10.1038/nrrheum.2014.172
LYME ARTHRITIS
Immune surveillance stops joint-invading Borrelia in mice Why don’t mice get lyme arthritis? New research led by Paul Kubes suggests immune surveillance by invariant natural killer T (iNKT) cells, which are more abundant in the joints of mice than humans, blocks the Lyme-disease inducing pathogen Borrelia burgdorferi from entering the joints. The findings are consistent with previous work by the same group and others, which showed that B. burgdorferi burden was 25-fold higher in the joints of mice deficient in iNKT cells compared with wild-type mice; notably, no other organs
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were affected in this way, indicating some unique quality of the joint environment. In the present study, the investigators used spinning-disk confocal intravital microscopy to visualize the distribution and behaviour of CXCR6+ cells, 60–70% of which are iNKT cells, in mouse tissues. They observed that iNKT cells in the liver, where they are most abundant, localized inside blood vessels and were seen to ‘crawl’ in a random pattern. By contrast, imaging of knee joint tissue revealed what Kubes describes as “very dramatic localization of iNKT cells surrounding joint blood vessels.” The majority of these extravascular knee joint iNKT cells were stationary in vivo. iNKT cells were also detected in human knee joint tissue, albeit fewer in number compared with mice. The investigators then observed in mice that extravascular iNKT cells interact directly with B. burgdorferi at the vessel wall, limiting the dissemination of the spirochaete into the joint. iNKT cells were no longer stationary but increased
NATURE REVIEWS | RHEUMATOLOGY
their motility after B. burgdorferi infection. Interaction with iNKT cells left B. burgdorferi immobilized; in comparison, far greater numbers of motile spirochaetes were seen in the joint tissue of mice deficient in iNKT cells. In vitro, iNKT cells isolated from mouse joints had cytotoxic effects on B. burgdorferi that the investigators determined to be granzyme-dependent. However, this cytotoxicity was not seen with spleen or liver iNKT cells. Kubes suggests the findings relate not only to susceptibility to Lyme arthritis but also its treatment. “We would like to test drugs that can stimulate iNKT cells in the joint as a potential therapy in humans with persistent Lyme arthritis.” Sarah Onuora Original article Lee, W. Y. et al. Invariant natural killer T cells act as an extravascular cytotoxic barrier for jointinvading Lyme Borrelia. Proc. Natl Acad. Sci. doi:10.1073/ pnas.1404769111
VOLUME 10 | NOVEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved
LYME ARTHRITIS
Immune surveillance stops joint-invading Borrelia in mice Why don’t mice get lyme arthritis? New research led by Paul Kubes suggests immune surveillance by invariant natural killer T (iNKT) cells, which are more abundant in the joints of mice than humans, blocks the Lyme-disease inducing pathogen Borrelia burgdorferi from entering the joints. The findings are consistent with previous work by the same group and others, which showed that B. burgdorferi burden was 25-fold higher in the joints of mice deficient in iNKT cells compared with wild-type mice; notably, no other organs
N
P
G
were affected in this way, indicating some unique quality of the joint environment. In the present study, the investigators used spinning-disk confocal intravital microscopy to visualize the distribution and behaviour of CXCR6+ cells, 60–70% of which are iNKT cells, in mouse tissues. They observed that iNKT cells in the liver, where they are most abundant, localized inside blood vessels and were seen to ‘crawl’ in a random pattern. By contrast, imaging of knee joint tissue revealed what Kubes describes as “very dramatic localization of iNKT cells surrounding joint blood vessels.” The majority of these extravascular knee joint iNKT cells were stationary in vivo. iNKT cells were also detected in human knee joint tissue, albeit fewer in number compared with mice. The investigators then observed in mice that extravascular iNKT cells interact directly with B. burgdorferi at the vessel wall, limiting the dissemination of the spirochaete into the joint. iNKT cells were no longer stationary but increased
NATURE REVIEWS | RHEUMATOLOGY
their motility after B. burgdorferi infection. Interaction with iNKT cells left B. burgdorferi immobilized; in comparison, far greater numbers of motile spirochaetes were seen in the joint tissue of mice deficient in iNKT cells. In vitro, iNKT cells isolated from mouse joints had cytotoxic effects on B. burgdorferi that the investigators determined to be granzyme-dependent. However, this cytotoxicity was not seen with spleen or liver iNKT cells. Kubes suggests the findings relate not only to susceptibility to Lyme arthritis but also its treatment. “We would like to test drugs that can stimulate iNKT cells in the joint as a potential therapy in humans with persistent Lyme arthritis.” Sarah Onuora Original article Lee, W. Y. et al. Invariant natural killer T cells act as an extravascular cytotoxic barrier for jointinvading Lyme Borrelia. Proc. Natl Acad. Sci. doi:10.1073/ pnas.1404769111
VOLUME 10 | NOVEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved
