| First Author | Sullivan JA | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 4 | Pages | 1039-1051.e5 |
| PubMed ID | 31995748 | Mgi Jnum | J:287437 |
| Mgi Id | MGI:6415820 | Doi | 10.1016/j.celrep.2019.12.081 |
| Citation | Sullivan JA, et al. (2020) Treg-Cell-Derived IL-35-Coated Extracellular Vesicles Promote Infectious Tolerance. Cell Rep 30(4):1039-1051.e5 |
| abstractText | Interleukin-35 (IL-35) is an immunosuppressive cytokine composed of Epstein-Barr-virus-induced protein 3 (Ebi3) and IL-12alpha chain (p35) subunits, yet the forms that IL-35 assume and its role in peripheral tolerance remain elusive. We induce CBA-specific, IL-35-producing T regulatory (Treg) cells in Treg(Ebi3WT) C57BL/6 reporter mice and identify IL-35 producers by expression of Ebi3(TdTom) gene reporter plus Ebi3 and p35 proteins. Curiously, both subunits of IL-35 are displayed on the surface of tolerogen-specific Foxp3(+) and Foxp3(neg) (iTr35) T cells. Furthermore, IL-35 producers, although rare, secrete Ebi3 and p35 on extracellular vesicles (EVs) targeting a 25- to 100-fold higher number of T and B lymphocytes, causing them to acquire surface IL-35. This surface IL-35 is absent when EV production is inhibited or if Ebi3 is genetically deleted in Treg cells. The unique ability of EVs to coat bystander lymphocytes with IL-35, promoting exhaustion in, and secondary suppression by, non-Treg cells identifies a novel mechanism of infectious tolerance. |
