| Autor: |
Victor, Aaron R., Nalin, Ansel P., Dong, Wenjuan, McClory, Susan, Wei, Min, Mao, Charlene, Kladney, Raleigh D., Youssef, Youssef, Chan, Wing Keung, Briercheck, Edward L., Hughes, Tiffany, Scoville, Steven D., Pitarresi, Jason R., Chen, Charlie, Manz, Sarah, Wu, Lai-Chu, Zhang, Jianying, Ostrowski, Michael C., Freud, Aharon G., Leone, Gustavo W., Caligiuri, Michael A., Yu, Jianhua |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Popis: |
Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in the presence of commensal bacteria, but activating immune defenses in response to microbial pathogens. ILC3s are a robust source of IL-22, a cytokine critical for stimulating the anti-microbial response. We sought to identify cytokines that can promote proliferation and induce or maintain IL-22 production by ILC3s and determine a molecular mechanism for this process. We identified IL-18 as a cytokine that cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well as induce and maintain IL-22 production. To determine a mechanism of action, we examined the NF-κB pathway, which is activated by IL-18 signaling. We found that the NF-κB complex signaling component, p65, binds to the proximal region of the IL22 promoter and promotes transcriptional activity. Finally, we observed that CD11c+ dendritic cells expressing IL-18 are found in close proximity to ILC3s in human tonsils in situ. Therefore, we identify a new mechanism by which human ILC3s proliferate and produce IL-22, and identify NF-κB as a potential therapeutic target to be considered in pathologic states characterized by overproduction of IL-18 and/or IL-22. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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