| First Author | Wagage S | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 4 | Pages | 1661-70 |
| PubMed ID | 24403534 | Mgi Jnum | J:209400 |
| Mgi Id | MGI:5567059 | Doi | 10.4049/jimmunol.1300497 |
| Citation | Wagage S, et al. (2014) The aryl hydrocarbon receptor promotes IL-10 production by NK cells. J Immunol 192(4):1661-70 |
| abstractText | The cytokine IL-10 has an important role in limiting inflammation in many settings, including toxoplasmosis. In the present studies, an IL-10 reporter mouse was used to identify the sources of this cytokine following challenge with Toxoplasma gondii. During infection, multiple cell types expressed the IL-10 reporter but NK cells were a major early source of this cytokine. These IL-10 reporter(+) NK cells expressed high levels of the IL-12 target genes T-bet, KLRG1, and IFN-gamma, and IL-12 depletion abrogated reporter expression. However, IL-12 signaling alone was not sufficient to promote NK cell IL-10, and activation of the aryl hydrocarbon receptor (AHR) was also required for maximal IL-10 production. NK cells basally expressed the AHR, relevant chaperone proteins, and the AHR nuclear translocator, which heterodimerizes with the AHR to form a competent transcription factor. In vitro studies revealed that IL-12 stimulation increased NK cell AHR levels, and the AHR and AHR nuclear translocator were required for optimal production of IL-10. Additionally, NK cells isolated from T. gondii-infected Ahr(-/-) mice had impaired expression of IL-10, which was associated with increased resistance to this infection. Taken together, these data identify the AHR as a critical cofactor involved in NK cell production of IL-10. |
