| First Author | Leavenworth JW | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 1 | Pages | 96-106 |
| PubMed ID | 25436971 | Mgi Jnum | J:222609 |
| Mgi Id | MGI:5644924 | Doi | 10.1038/ni.3050 |
| Citation | Leavenworth JW, et al. (2015) A p85alpha-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nat Immunol 16(1):96-106 |
| abstractText | Follicular helper T cells (TFH cells) and follicular regulatory T cells (TFR cells) regulate the quantity and quality of humoral immunity. Although both cell types express the costimulatory receptor ICOS and require the transcription factor Bcl-6 for their differentiation, the ICOS-dependent pathways that coordinate their responses are not well understood. Here we report that activation of ICOS in CD4(+) T cells promoted interaction of the p85alpha regulatory subunit of the signaling kinase PI(3)K and intracellular osteopontin (OPN-i), followed by translocation of OPN-i to the nucleus, its interaction with Bcl-6 and protection of Bcl-6 from ubiquitin-dependent proteasome degradation. Post-translational protection of Bcl-6 by OPN-i was essential for sustained responses of TFH cells and TFR cells and regulation of the germinal center B cell response to antigen. Thus, the p85alpha-OPN-i axis represents a molecular bridge that couples activation of ICOS to Bcl-6-dependent functional differentiation of TFH cells and TFR cells; this suggests new therapeutic avenues to manipulate the responses of these cells. |
