| First Author | Barik S | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 8 | Pages | 2039-2045 |
| PubMed ID | 32917785 | Mgi Jnum | J:303588 |
| Mgi Id | MGI:6502464 | Doi | 10.4049/jimmunol.2000614 |
| Citation | Barik S, et al. (2020) Type II Cytokines Fine-Tune Thymic T Cell Selection to Offset Murine Central Nervous System Autoimmunity. J Immunol 205(8):2039-2045 |
| abstractText | Early thymic progenitors (ETPs) are bone marrow-derived hematopoietic stem cells that remain multipotent and give rise to a variety of lineage-specific cells. Recently, we discovered a subset of murine ETPs that expresses the IL-4Ralpha/IL-13Ralpha1 heteroreceptor (HR) and commits only to the myeloid lineage. This is because IL-4/IL-13 signaling through the HR inhibits their T cell potential and enacts commitment of HR(+)ETPs to thymic resident CD11c(+)CD8alpha(+) dendritic cells (DCs). In this study, we discovered that HR(+)-ETP-derived DCs function as APCs in the thymus and promote deletion of myelin-reactive T cells. Furthermore, this negative T cell selection function of HR(+)-ETP-derived DCs sustains protection against experimental allergic encephalomyelitis, a mouse model for human multiple sclerosis. These findings, while shedding light on the intricacies underlying ETP lineage commitment, reveal a novel, to our knowledge, function by which IL-4 and IL-13 cytokines condition thymic microenvironment to rheostat T cell selection and fine-tune central tolerance. |
