期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00880-2
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资金
- National Institutes of Health [R01-AI066008, R56-AI066008]
- National Cancer Institute of the National Institutes of Health [P30CA033572]
Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome mediated by pathogenic CD4+ T and B cells, but the function of extrafollicular and germinal center CD4(+) T and B interactions in cGVHD pathogenesis remains largely unknown. Here we show that extrafollicular CD4(+) T and B interactions are sufficient for inducing cGVHD, while germinal center formation is dispensable. The pathogenesis of cGVHD is associated with the expansion of extrafollicular CD44(hi)CD62(lo)PSGL-1(lo)CD4(+) (PSGL-1(lo)CD4(+)) T cells. These cells express high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and ameliorates cGVHD. Expansion of PSGL-1loCD4(+) T cells is also prevented by BCL6 or Stat3 deficiency in donor CD4(+) T cells, with the induction of cGVHD ameliorated by BCL6 deficiency and completely suppressed by Stat3 deficiency in donor CD4(+) T cells. These results support that Stat3 -and BCL6-dependent extrafollicular CD4(+) T and B interactions play critical functions in the pathogenesis of cGVHD.
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