| First Author | Jiang G | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 4 | Pages | 599-607 |
| PubMed ID | 24374967 | Mgi Jnum | J:211961 |
| Mgi Id | MGI:5577023 | Doi | 10.1189/jlb.0613337 |
| Citation | Jiang G, et al. (2014) HMGB1 is an early and critical mediator in an animal model of uveitis induced by IRBP-specific T cells. J Leukoc Biol 95(4):599-607 |
| abstractText | It is largely unknown how invading autoreactive T cells initiate the pathogenic process inside the diseased organ in organ-specific autoimmune disease. In this study, we used a chronic uveitis disease model in mice--EAU--induced by adoptive transfer of uveitogenic IRBP-specific T cells and showed that HMGB1, an important endogenous molecule that serves as a danger signal, was released rapidly from retinal cells into the ECM and intraocular fluid in response to IRBP-specific T cell transfer. HMGB1 release required direct cell-cell contact between retinal cells and IRBP-specific T cells and was an active secretion from intact retinal cells. Administration of HMGB1 antagonists inhibited severity of EAU significantly via mechanisms that include inhibition of IRBP-specific T cell proliferation and their IFN-gamma and IL-17 production. The inflammatory effects of HMGB1 may signal the TLR/MyD88 pathway, as MyD88(-/-) mice had a high level of HMGB1 in the eye but did not develop EAU after IRBP-specific T cell transfer. Our study demonstrates that HMGB1 is an early and critical mediator of ocular inflammation initiated by autoreactive T cell invasion. |
