| First Author | Fukushima Y | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 12 | Pages | 111373 |
| PubMed ID | 36130493 | Mgi Jnum | J:329298 |
| Mgi Id | MGI:7343475 | Doi | 10.1016/j.celrep.2022.111373 |
| Citation | Fukushima Y, et al. (2022) cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells. Cell Rep 40(12):111373 |
| abstractText | With age, senescence-associated (SA) CD4(+) T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity. |
