| First Author | Bruhs A | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 2 | Pages | 435-444 |
| PubMed ID | 25251932 | Mgi Jnum | J:218044 |
| Mgi Id | MGI:5616482 | Doi | 10.1038/jid.2014.419 |
| Citation | Bruhs A, et al. (2015) Activation of the arylhydrocarbon receptor causes immunosuppression primarily by modulating dendritic cells. J Invest Dermatol 135(2):435-44 |
| abstractText | UVR suppresses the immune system in an antigen-specific manner via induction of regulatory T cells (Tregs). The specific immunosuppression by UVR harbors therapeutic potential but is associated with UVR-induced DNA damage, requiring the identification of other triggers inducing the same immunosuppressive effects without DNA damage. The aryl hydrocarbon receptor (AhR) was identified as a molecular target for UVR and its activation to be involved in UVR-induced immunosuppression. Accordingly, the AhR agonist 4-n-nonylphenol (NP) suppressed sensitization and induced Treg similar to UVR. Here we show that antigen-presenting cells are critically involved in AhR-induced immunosuppression. Injection of hapten-coupled dendritic cells (DCs) treated with NP into mice did not result in sensitization but induced Treg. NP induced the release of IL-2 by DC that subsequently triggered the release of IL-10. NP upregulated the negative regulatory molecule B7-H4 via the release of IL-2 that was functionally relevant as inhibition of B7-H4 prevented the induction of Treg. Together, this indicates that activation of the AhR switches antigen-presenting cells from a stimulatory into a regulatory phenotype, ultimately inducing Treg. Thus, AhR agonists may represent an alternative to suppress the immune system like UVR but without causing the adverse effects of UVR including DNA damage. |
