Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

Kotschenreuther, Konstantin; Waqué, Iris; Yan, Shuaifeng; Meyer, Anja; Haak, T.; Tresckow, Julia von; Schiller, Joanna; Gloyer, Lydia; Dittrich-Salamon, Mara; Kofler, David M.

doi:10.1038/s41423-020-0437-4

Cited by 10 publications

(7 citation statements)

References 6 publications

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“…68 Interestingly, in vitro culture in the presence of CBD significantly increased Th17 cell differentiation in CD4+ T cells from the peripheral blood of patients with RA. 111 There are currently no randomised clinical trials investigating the use of cannabis in the treatment of RA, partly because of the availability of effective biological antiinflammatory agents in the therapeutic armamentarium. 112 However, one preliminary randomised, placebo-controlled study has assessed the efficacy, tolerability and safety of five weeks' treatment with a synthetic TCH analogue in 58 RA patients, and found that pain was significantly reduced and disease activity significantly suppressed.…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Cannabis and Autoimmunity: Possible Mechanisms of Action

Giorgi

Marotto

Batticciotto

et al. 2021

ITT

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Medical cannabis (MC) describes the usually inhaled or ingested use of a cannabis plant or cannabis extract for medicinal purposes. The action of whole cannabis plants is extremely complex because their large number of active compounds not only bind to a plethora of different receptors but also interact with each other both synergistically and otherwise. Renewed interest in the medicinal properties of cannabis has led to increasing research into the practical uses of cannabis derivatives, and it has been found that the endocannabinoid system (particularly CB2 receptor activation) is a possible target for the treatment of inflammatory and the autoimmune diseases related to immune cell activation. However, in vivo findings still lack, creating difficulties in applying translational cannabinoid research to human immune functions. In this review, we summarized the main mechanisms of action of medical cannabis plant especially regarding the immune system and the endocannabinoid system, looking at preliminary clinical data in three most important autoimmune diseases of three different specialities: rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.

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Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Cannabis and Autoimmunity: Possible Mechanisms of Action

Giorgi

Marotto

Batticciotto

et al. 2021

ITT

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“…Cannabaceae, an annual herbaceous crop, has been widely cultivated for fiber, food, and medicine for thousands of years ( Pain, 2015 ; Guo et al, 2018 ). Hemp [cultivated Cannabis with lower Δ 9 -tetrahydrocannabinol (THC)] has received increasing attention in recent years, especially for cannabinoids (CBD) ( Lv et al, 2019 ; Kotschenreuther et al, 2020 ). CBD is a component of cannabis with no psychoactive properties ( Vrechi et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Self-Assembly System Based on Cyclodextrin for Targeted Delivery of Cannabidiol

Zhu

Zhang

et al. 2021

Front. Chem.

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Cannabidiol (CBD) is one specific kind of the cannabinoid in Cannabis sativa L with a wide range of pharmacological activities. However, the poor water solubility and specificity of CBD limits its application in pharmaceutical field. For solving these problems, in this work, we successfully prepared a targeted carrier by grafting biotin (BIO) onto ethylenediamine-β-Cyclodextrin (EN-CD) in a single step to generate a functionalized supramolecule, named BIO-CD. Subsequently, an amantadine-conjugated cannabinoids (AD-CBD) was prepared and self-assembled with the BIO-CD. A series of methods were used to characterize the inclusion behavior and physicochemical properties of AD-CBD and BIO-CD. The results showed that AD-CBD entered the cavity of BIO-CD and formed a 1:1 host-guest inclusion complex. MTT assay and confocal laser scanning microscopy (CLSM) revealed that the targeting effect and anticancer activity of AD-CBD/BIO-CD inclusion complex against three human cancer cell lines were higher than BIO-CD, AD-CBD and free CBD. Moreover, the inclusion complex could release drugs under weakly acidic conditions. These results demonstrated that AD-CBD/BIO-CD inclusion complex possess excellent targeted and anticancer activity, which is hopeful to be applied in clinic as a new therapeutic approach.

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“…IGF ligands possess the ability to skew Th17 programming towards the expression of pro-inflammatory genes with concurrent inhibition of anti-inflammatory genes; one proposed mechanism by which this is accomplished is an increase in HIF-1α dependent gene expression ( 108 ). Interestingly, continued research has been able to show that lifestyle choices, such as a high-salt diet or cannabinoid consumption might be able to skew this ratio in favor of Th17 cells ( 109 , 110 ). Numerous studies have been able to show that the Th17/T reg ratio is skewed in favor of Th17 cells in RA when compared to healthy controls.…”

Section: Th17/t Reg Balancementioning

confidence: 99%

Migration and homeostasis of regulatory T cells in rheumatoid arthritis

2022

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Regulatory T (Treg) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of Treg cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. Treg cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of Treg cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in Treg cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of Treg cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced Treg cell trafficking. Another protein which facilitates Treg cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in Treg cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of Treg cell migration and review the current knowledge about impaired Treg cell homeostasis in RA.

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Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

Cited by 10 publications

References 6 publications

Cannabis and Autoimmunity: Possible Mechanisms of Action

Cannabis and Autoimmunity: Possible Mechanisms of Action

Self-Assembly System Based on Cyclodextrin for Targeted Delivery of Cannabidiol

Migration and homeostasis of regulatory T cells in rheumatoid arthritis

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