Biology subjects

Collins, C. B.

Publications and source records attributed to Collins, C. B..

4 recordsLinked to original sources

bioRxiv2026

Cannabinoid CB2 receptor activation drives glucose uptake, shifting T cell metabolism.

Cannabinoid receptor 2 (CB2R) is highly expressed on immune cells, but its role in T cell metabolism remains unclear. Here, we show that CB2R activation rapidly increases glucose uptake in human Jurkat T cells and drives a broader metabolic reprogramming away from glycolysis toward oxidative metabolism and the pentose phosphate pathway. Pharmacological CB2R activation increased mitochondrial mass, spare respiratory capacity, proton leak, and NADPH production, while CB2R inverse agonism produced the opposite effects. These metabolic changes were accompanied by upregulation of key pentose phosphate pathway enzymes, including GALT and TALDO1, and were abolished in CNR2-deficient cells, confirming receptor dependence. In primary human lamina propria mononuclear cells, CB2R signalling also influenced memory and gut-homing-associated T cell phenotypes, including integrin 4{beta}7 expression. Together, these findings identify CB2R as a regulator of T cell bioenergetics and suggest that cannabinoid signalling may promote metabolic states linked to memory and tissue-homing functions in chronic intestinal inflammation. Brief SummaryO_LICB2R agonist-mediated increased glucose uptake in human T cells is lost in CNR2-deficient cells, suggesting that the response is receptor-dependent. C_LIO_LICB2R activation rewires T-cell metabolism toward increased oxidative phosphorylation, spare respiratory capacity, mitochondrial mass, and pentose phosphate pathway metabolism, including higher NADPH and PPP-enzyme expression. C_LIO_LIIn primary human intestinal immune cells, CB2R also promotes gut-homing and memory-associated T-cell phenotypes, including 4{beta}7 and CD103 integrin induction ex vivo, suggesting a possible link to exacerbation of chronic intestinal inflammation. C_LI

immunology↗

bioRxiv2025

Cannabinoid CB2R regulates T cell gut-homing in preclinical Crohns model.

Leukocyte trafficking is a critical step in development of chronic intestinal diseases such as Crohns disease. While strategies that block gut-homing have yielded partial success, this disease remains uncurable leaving an unmet clinical need. This is the first paper to describe a role for cannabinoid receptor two (CB2R) signalling in promoting retinoic acid-mediated induction of the gut-homing associated integrin heterodimer 4{beta}7. Using in vitro and in vivo models, we characterised the effects of pharmacological CB2R agonists and inverse agonists on T cell homing receptor expression and transmigration across gut-associated endothelial barriers. This ERK-dependent process coincides with increased T cell adherence in response to CB2R agonism with JWH133. These effects were reversed with an inverse agonist GP-1a in a CB2R dependent manner. Selective deletion of CB2R using CRISPR in vitro or CD4Cre/+ floxed mice in vivo resulted in impaired endothelial cell adherence and decreased diapedesis into the ileal lamina propria. T cell-specific deletion of cnr2, the gene encoding CB2R, attenuated chronic murine ileitis characterised by decreased naive T cell infiltration and loss of tissue architecture in 20wk TNF{Delta}ARE/+mice. This study supports further therapeutic development of CB2R-blocking drugs for the treatment of inflammatory bowel disease.

immunology↗

bioRxiv2024

Priming lymphocyte responsiveness and differential T cell signaling in pediatric IBD patients with Cannabis use.

The prevalence of inflammatory bowel disease (IBD) has increased dramatically in recent years, particularly in pediatric populations. Successful remission with current therapies is limited and often transient, leading patients to seek alternative therapies for symptom relief, including the use of medical marijuana (Cannabis sativa). However, chronic cannabis use among IBD patients is associated with increased risk for surgical interventions. Therefore, determining the direct impact of cannabis use on immune modulation in IBD patients is of critical importance. Peripheral blood mononuclear cells of cannabis using and non-using pediatric IBD patients were phenotyped by flow cytometry and functionally assessed for their cytokine production profile. A phospho-kinase array was also performed to better understand changes in immune responses. Results were then compared with serum phytocannabinoid profiles of each patient to identify cannabinoid-correlated changes in immune responses.Results demonstrated elevated levels of a myriad of pro-inflammatory cytokines in users versus non-users. Differences in signaling cascades of activated T cells between users and non-users were also observed. A number of anti-inflammatory cytokines were inversely correlated with serum phytocannabinoids. These results suggest that cannabis exposure, which can desensitize cannabinoid receptors, may prime pro-inflammatory pathways in pediatric IBD patients. Article SummaryThis observational study examines the impact of chronic cannabis use on peripheral immune cell function in adolescent IBD patients from Childrens Hospital Colorado. Cannabis users displayed altered T cell phenotype, increased pro-inflammatory cytokine release and dephosphorylation of protective protein kinases.

immunology↗

bioRxiv2019

Radiofrequency Remote Control of Thermolysin Activity

Nearly all biological processes are regulated by enzymes, precise control over specific enzymes could create the potential for controlling cellular processes remotely. We have successfully shown that the thermophilic enzyme thermolysin can be remotely activated in 17.76 MHz radiofrequency (RF) fields when covalently attached to 6.1 nm gold coated magnetite nanoparticles. Without raising the bulk solution temperature, we observe enzyme activity as if the solution was 16 {+/-} 2 {degrees}C warmer in RF fields, or an increase in enzymatic rate of 129 {+/-} 8%. Kinetics studies show that the activity increase of the enzyme is consistent with the induced fit of a hot enzyme with cold substrate.

biophysics↗