| First Author | Deng R | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 978 |
| PubMed ID | 29042531 | Mgi Jnum | J:257196 |
| Mgi Id | MGI:6100764 | Doi | 10.1038/s41467-017-00880-2 |
| Citation | Deng R, et al. (2017) Extrafollicular CD4(+) T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease. Nat Commun 8(1):978 |
| abstractText | 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-1(lo)CD4(+) 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.Chronic graft-versus-host disease (cGVHD) is mediated by specific CD4 and B cells, but the relative contribution of extrafollicular and germinal centre (GC) T-B interaction is unclear. Here the authors show that the extrafollicular expansion of a specific CD4 T subset is sufficient for inducing cGVHD while GC is dispensable. |
