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. 2016 Nov 4;5(12):e1254854. doi: 10.1080/2162402X.2016.1254854

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© 2016 The Author(s). Published with license by Taylor & Francis Group, LLC

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

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Figure 2. — RORγ agonists enhance Type 17 differentiation and cytokine production. (A) RORγ agonist LYC-53772 increased Type 17 cytokines when added to both Th17 and Tc17 differentiation cultures. LYC-53772 vs. vehicle, p < 0.007 for Th17 and p < 0.03 for Th17 and Tc17, respectively. Data represent mean ± SD of biological quadruplicates. (B) LYC-53772 increased the percentage of CD4⁺IL-17A⁺ (Th17, left) and CD8⁺IL-17A⁺ (Tc17, right) cells with minimal effects on their production of IFNγ (representative flow graph). (C) Elevated IL-17A expression was dependent on RORγ. IL-17A mRNA was assayed by qPCR. Data represent mean ± SD of biological triplicates. (D) RORγ agonist LYC-54143 increased cytokine production in human PBMCs polarized under Type 17 conditions. LYC-54143 vs. vehicle, p < 0.03 for IL-17A, IL-17F, or IL-22, p = 0.5 for IFNγ. Data represent mean ± SD of biological duplicates from one healthy donor. Similar results were obtained for > 4 healthy donors. (E) LYC-53772 decreased the percentage of FOXP3⁺ cells during differentiation of murine Treg cells. *p = 1.6 × 10⁻⁷ LYC-53772 vs. Vehicle. (F) LYC-54143 decreased FOXP3⁺ cells during Type 17 differentiation of human PBMCs. *p = 0.009, LYC-54143 vs. Vehicle. Data represent mean ± SD of biological triplicates from one healthy donor. Similar results were obtained for three healthy donors. (G) LYC-54143 decreased the percentage of dead murine Type 17 T cells after differentiation and resting for 3 days. *p = 0.0001, LYC-54143 vs. Vehicle. Data represent mean ± SD of biological triplicates. LYC-53772 was used at 10 µM and LYC-54143 at 5 µM.