Rethinking EAE pathogenesis
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《实验药学杂志》
CD4+ T cells cultured in vitro with IL-23 (), but not IL-12 () induce EAE pathogenesis.
Th1 cells have long been thought to mediate the pathogenesis of experimental autoimmune encephalitis (EAE), a mouse model for multiple sclerosis. But Langrish et al. now identify a new subset of T cells as the driving force behind brain inflammation in EAE (page 233).
Previous thinking on EAE culprits has focused on Th1 CD4+ T cells and their distinctive product IFN-, both of which are found at EAE inflammation sites. But the details were confused by the biology of p40—a subunit shared by both IL-12 (an inducer of Th1 cells) and IL-23. This group showed recently that EAE is suppressed after p40 inactivation because of the loss of IL-23 not IL-12.
The authors now explain the pathogenic effect of IL-23 by showing that this cytokine induces a newly recognized subset of CD4+ T cells, which produces large amounts of IL-17 and IL-6 but very little IFN-. These T cells and IFN-–producing Th1 cells both invaded the CNS during EAE in wild-type mice, but only IFN-–producing Th1 cells were found in the CNS in mice lacking IL-23. Furthermore, T cells cultured in vitro with IL-23, but not those cultured with IL-12, could transfer the disease to naive mice.
How these cells induce disease is not completely understood. IL-17 appears to be a key player, as blocking IL-17 in wild-type mice partially reversed disease. IL-17 is known to drive the production of inflammatory cytokines from memory T cells, and IL-23 induces proliferation of these cells—both of which may amplify inflammation. Whatever the mechanism, this study appears to exonerate traditional Th1 cells as the main players in the pathogenesis of EAE.(Heather L. Van Epps)
Th1 cells have long been thought to mediate the pathogenesis of experimental autoimmune encephalitis (EAE), a mouse model for multiple sclerosis. But Langrish et al. now identify a new subset of T cells as the driving force behind brain inflammation in EAE (page 233).
Previous thinking on EAE culprits has focused on Th1 CD4+ T cells and their distinctive product IFN-, both of which are found at EAE inflammation sites. But the details were confused by the biology of p40—a subunit shared by both IL-12 (an inducer of Th1 cells) and IL-23. This group showed recently that EAE is suppressed after p40 inactivation because of the loss of IL-23 not IL-12.
The authors now explain the pathogenic effect of IL-23 by showing that this cytokine induces a newly recognized subset of CD4+ T cells, which produces large amounts of IL-17 and IL-6 but very little IFN-. These T cells and IFN-–producing Th1 cells both invaded the CNS during EAE in wild-type mice, but only IFN-–producing Th1 cells were found in the CNS in mice lacking IL-23. Furthermore, T cells cultured in vitro with IL-23, but not those cultured with IL-12, could transfer the disease to naive mice.
How these cells induce disease is not completely understood. IL-17 appears to be a key player, as blocking IL-17 in wild-type mice partially reversed disease. IL-17 is known to drive the production of inflammatory cytokines from memory T cells, and IL-23 induces proliferation of these cells—both of which may amplify inflammation. Whatever the mechanism, this study appears to exonerate traditional Th1 cells as the main players in the pathogenesis of EAE.(Heather L. Van Epps)