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Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype

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Abstract

Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis. We found that reactivation by MOG35-55 of MOG35-55-specific encephalitogenic T cells (cells that induce Experimental Autoimmune Encephalitis when injected to mice) in the presence of spleen derived antigen presenting cells led to a large increase in IL-17 production and secretion. In addition, we found that the cannabinoids CBD and THC dose-dependently (at 0.1–5 μM) suppressed the production and secretion of this cytokine. Moreover, the mRNA and protein of IL-6, a key factor in Th17 induction, were also decreased. Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors. In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.

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Acknowledgments

This work was supported by the Dr Miriam and Sheldon G. Adelson Medical Research Foundation. A.J. is supported by the Israeli Ministry for Absorption in Science.

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Authors and Affiliations

  1. The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ewa Kozela, Ana Juknat, Neta Rimmerman & Zvi Vogel

  2. Immunology Department, Weizmann Institute of Science, Rehovot, Israel

    Nathali Kaushansky & Avraham Ben-Nun

  3. Neurobiology Department, Weizmann Institute of Science, Rehovot, Israel

    Zvi Vogel

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  1. Ewa Kozela
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  2. Ana Juknat
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Correspondence to Ewa Kozela.

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Kozela, E., Juknat, A., Kaushansky, N. et al. Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype. J Neuroimmune Pharmacol 8, 1265–1276 (2013). https://doi.org/10.1007/s11481-013-9493-1

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