Antigen-specific immunotolerance limits the expansion of self-reactive T cells involved in autoimmune diseases. Here, we show that the E3 ubiquitin ligase Cbl-b is upregulated in T cells after tolerizing signals. Loss of Cbl-b in mice results in impaired induction of T cell tolerance both in vitro and in vivo. Importantly, rechallenge of Cbl-b mutant mice with the tolerizing antigen results in massive lethality. Moreover, ablation of Cbl-b resulted in exacerbated autoimmunity. Mechanistically, loss of Cbl-b rescues reduced calcium mobilization of anergic T cells, which was attributed to Cbl-b-mediated regulation of PLCγ-1 phosphorylation. Our results show a critical role for Cbl-b in the regulation of peripheral tolerance and anergy of T cells.
CITATION STYLE
Jeon, M. S., Atfield, A., Venuprasad, K., Krawczyk, C., Sarao, R., Elly, C., … Penninger, J. M. (2004). Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity, 21(2), 167–177. https://doi.org/10.1016/j.immuni.2004.07.013
Mendeley helps you to discover research relevant for your work.