| First Author | Hervé J | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 7 | Pages | 3163-71 |
| PubMed ID | 23420884 | Mgi Jnum | J:194464 |
| Mgi Id | MGI:5473908 | Doi | 10.4049/jimmunol.1201391 |
| Citation | Herve J, et al. (2013) beta2-Adrenoreceptor Agonist Inhibits Antigen Cross-Presentation by Dendritic Cells. J Immunol 190(7):3163-71 |
| abstractText | Despite widespread usage of beta-adrenergic receptor (AR) agonists and antagonists in current clinical practice, our understanding of their interactions with the immune system is surprisingly sparse. Among the AR expressed by dendritic cells (DC), beta2-AR can modify in vitro cytokine release upon stimulation. Because DC play a pivotal role in CD8(+) T cell immune responses, we examined the effects of beta2-AR stimulation on MHC class I exogenous peptide presentation and cross-presentation capacities. We demonstrate that beta2-AR agonist-exposed mature DC display a reduced ability to cross-present protein Ags while retaining their exogenous peptide presentation capability. This effect is mediated through the nonclassical inhibitory G (Galphai/0) protein. Moreover, inhibition of cross-presentation is neither due to reduced costimulatory molecule expression nor Ag uptake, but rather to impaired phagosomal Ag degradation. We observed a crosstalk between the TLR4 and beta2-AR transduction pathways at the NF-kappaB level. In vivo, beta2-AR agonist treatment of mice inhibits Ag protein cross-presentation to CD8(+) T cells but preserves their exogenous MHC class I peptide presentation capability. These findings may explain some side effects on the immune system associated with stress or beta-agonist treatment and pave the way for the development of new immunomodulatory strategies. |
