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1. HIF-2α-dependent induction of miR-29a restrains TH1 activity during T cell dependent colitis

Author

Czopik, Agnieszka K., McNamee, Eóin N., Vaughn, Victoria, Huang, Xiangsheng, Bang, In Hyuk, Clark, Trent, Wang, Yanyu, Ruan, Wei, Nguyen, Tom, Masterson, Joanne C., Tak, Eunyoung, Frank, Sandra, Collins, Colm B., Li, Howard, Rodriguez-Aguayo, Cristian, Lopez-Berestein, Gabriel, Gerich, Mark E., Furuta, Glenn T., Yuan, Xiaoyi, Sood, Anil K., de Zoeten, Edwin F., and Eltzschig, Holger K.

Published
2024
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3. HIF-2α-dependent induction of miR-29a restrains TH1 activity during T cell dependent colitis.

Author

Czopik, Agnieszka K., McNamee, Eóin N., Vaughn, Victoria, Huang, Xiangsheng, Bang, In Hyuk, Clark, Trent, Wang, Yanyu, Ruan, Wei, Nguyen, Tom, Masterson, Joanne C., Tak, Eunyoung, Frank, Sandra, Collins, Colm B., Li, Howard, Rodriguez-Aguayo, Cristian, Lopez-Berestein, Gabriel, Gerich, Mark E., Furuta, Glenn T., Yuan, Xiaoyi, and Sood, Anil K.

Subjects
INFLAMMATORY bowel diseases, HYPOXIA-inducible factors, CELLULAR control mechanisms, CELL physiology, TRANSCRIPTION factors, T cells
Abstract

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4+ T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target of miR-29a) levels and exacerbated intestinal inflammation. Mice with miR-29a deficiency in T cells show enhanced intestinal inflammation. T cell-intrinsic overexpression of HIF-2α or delivery of miR-29a mimetic dampen TH1-driven colitis. In this work, we show a previously unrecognized function for hypoxia-dependent induction of miR-29a in attenuating TH1-mediated inflammation. Inflammatory intestinal lesions are often hypoxic, which results in the stabilization and activation of hypoxia-inducible-factors (HIF). Here authors show that in a mouse model of colitis, HIF-2α is specifically stabilized in CD4+ type 1T helper (TH1) cells, leading to the upregulation of miR-29a expression and suppression of TH1 cell function, which pathway is potentially targetable for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Heat shock factor 1 drives regulatory T-cell induction to limit murine intestinal inflammation

Author

Collins, Colm B., primary, Nguyen, Tom T., additional, Leddy, Robert S., additional, Alula, Kibrom M., additional, Yeckes, Alyson R., additional, Strassheim, Derek, additional, Aherne, Carol M., additional, Luck, Marisa E., additional, Karoor, Vijaya, additional, Jedlicka, Paul, additional, Pierce, Anson, additional, and de Zoeten, Edwin F., additional

Published
2023
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9. Interleukin 37 expression protects mice from colitis

Author

McNamee, Eóin N., Masterson, Joanne C., Jedlicka, Paul, McManus, Martine, Grenz, Almut, Collins, Colm B., Nold, Marcel F., Nold-Petry, Claudia, Bufler, Philip, Dinarello, Charles A., and Rivera-Nieves, Jesús

Published
2011

18. Cannabinoid Receptor-2 Ameliorates Inflammation in Murine Model of Crohn’s Disease

Author

Leinwand, Kristina L, primary, Jones, Ashleigh A, additional, Huang, Rick H, additional, Jedlicka, Paul, additional, Kao, Daniel J, additional, de Zoeten, Edwin F, additional, Ghosh, Soumita, additional, Moaddel, Ruin, additional, Wehkamp, Jan, additional, Ostaff, Maureen J, additional, Bader, Jutta, additional, Aherne, Carol M, additional, and Collins, Colm B, additional

Published
2017
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19. Pro-Inflammatory Cytokines Drive the Development of a Prothrombotic Platelet Phenotype in Inflammation and Aging

Author

Davizon-Castillo, Pavel, primary, Ashworth, Katrina, additional, Higa, Kelly, additional, Hernandez, Giovanny, additional, Acharya, Sumitra, additional, Campbell, Robert A., additional, Rondina, Matthew, additional, Collins, Colm B., additional, Donato, Anthony, additional, Lesniewski, Lisa, additional, DeGregori, James, additional, Holer, Michael, additional, Banda, Nirmal, additional, Di Paola, Jorge, additional, and Pietras, Eric Martin, additional

Published
2016
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20. Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Author

Neff, C. Preston, primary, Rhodes, Matthew E., additional, Arnolds, Kathleen L., additional, Collins, Colm B., additional, Donnelly, Jody, additional, Nusbacher, Nichole, additional, Jedlicka, Paul, additional, Schneider, Jennifer M., additional, McCarter, Martin D., additional, Shaffer, Michael, additional, Mazmanian, Sarkis K., additional, Palmer, Brent E., additional, and Lozupone, Catherine A., additional

Published
2016
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21. Retinoic Acid Attenuates Ileitis by Restoring the Balance between T-Helper 17 and T

Author

Collins, Colm B., Aherne, Carol M., Kominsky, Douglas, McNamee, Eóin N., Lebsack, Matthew D.P., Eltzschig, Holger, Jedlicka, Paul, and Rivera-Nieves, Jesús

Subjects
Mice, Knockout, Forkhead Transcription Factors, Mice, Inbred Strains, Tretinoin, Dendritic Cells, Ileitis, T-Lymphocytes, Regulatory, Article, Coculture Techniques, Mice, Inbred C57BL, Disease Models, Animal, Mice, Antigens, CD, Animals, Cytokines, Th17 Cells, Integrin alpha Chains, Cells, Cultured, Cell Proliferation
Abstract

Retinoic acid (RA), produced by intestinal epithelial cells (IECs) and dendritic cells (DCs) promotes the induction of regulatory T cells (Tregs) and decreases the induction of T-helper (Th)17 cells.We studied the roles of RA in mice that overproduce tumor necrosis factor (TNF) and develop chronic ileitis (TNF_ARE mice). We assessed the frequency and function of CD103+ DCs, Th17 cells, and Tregs by flow cytometry, and we measured expression of cytokines and retinaldehyde dehydrogenase (RALDH) enzymes in ileum samples, DCs, and IECs by real-time polymerase chain reaction. We quantified RA by electrochemical analysis and examined the effect of RA supplementation on TNF-induced ileitis using histologic, coculture, and suppression assays and flow cytometry.Numbers of CD103+ DCs decreased in the inflamed ilea of mice with chronic disease; RA synthetic machinery (RALDH1,2) was down-regulated. Nevertheless, the proportion of CD4+, CD25+, FoxP3+ Tregs increased, indicating an alternate source for RA. IECs responded to reduced levels of RA by up-regulating RALDH3 in vivo and in vitro. Net tissue levels of RA remained lower in TNF+ARE than wild-type mice, indicating that epithelial up-regulation of RALDH3 could not maintain adequate concentrations of RA, probably because of loss of IEC mass. RA supplementation significantly attenuated disease by increasing the number and function of CD103+ DCs and Tregs and reducing Th17 cells.Reduced levels of RA appear to induce IECs to up-regulate synthesis of RA. RA supplementation attenuates ileitis through its effects on CD103+ DCs, Tregs, and Th17 cells. RA supplementation might offer therapeutic benefit in Crohn's disease.

Published
2011

28. IFN-γ–Mediated Induction of an Apical IL-10 Receptor on Polarized Intestinal Epithelia

Author

Kominsky, Douglas J., primary, Campbell, Eric L., additional, Ehrentraut, Stefan F., additional, Wilson, Kelly E., additional, Kelly, Caleb J., additional, Glover, Louise E., additional, Collins, Colm B., additional, Bayless, Amanda J., additional, Saeedi, Bejan, additional, Dobrinskikh, Evgenia, additional, Bowers, Brittelle E., additional, MacManus, Christopher F., additional, Müller, Werner, additional, Colgan, Sean P., additional, and Bruder, Dunja, additional

Published
2014
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29. Alpha-1-antitrypsin Therapy Ameliorates Acute Colitis and Chronic Murine Ileitis

Author

Collins, Colm B., Aherne, Carol M., Ehrentraut, Stefan F., Gerich, Mark E., McNamee, Eóin N., McManus, Martine, Lebsack, Matthew D.P., Jedlicka, Paul, Azam, Tania, de Zoeten, Edwin F., Dinarello, Charles A., Rivera-Nieves, Jesus, Collins, Colm B., Aherne, Carol M., Ehrentraut, Stefan F., Gerich, Mark E., McNamee, Eóin N., McManus, Martine, Lebsack, Matthew D.P., Jedlicka, Paul, Azam, Tania, de Zoeten, Edwin F., Dinarello, Charles A., and Rivera-Nieves, Jesus

Abstract

Background: Fecal alpha-1-antitrypsin (AAT) clearance has been a marker of clinical disease severity in inflammatory bowel diseases (IBDs) for many years. Although AAT deficiency is more often associated with lung and liver pathologies, AAT-deficient patients with concomitant IBD have been shown to develop more aggressive disease and rapid progression to surgery. Although recent studies have highlighted the pleiotropic anti-inflammatory functions of AAT, including reducing proinflammatory cytokine production and suppressing immune cell activation, its potential therapeutic role in IBD has not been described. Methods: The therapeutic potential of human AAT administration was assessed in murine models of IBD including new-onset and established chemically induced colitis and spontaneous chronic murine ileitis. Histological assessment of inflammation, cytokine secretion profiling, and flow cytometric evaluation of inflammatory infiltrate were performed in each model. The effect of AAT on intestinal barrier function was also examined both in vitro and in vivo. Results: AAT attenuated inflammation in small and large intestinal IBD models through reduced secretion of proinflammatory cytokines, inflammatory cell infiltration, and reduced tissue injury. AAT also increased intestinal restitution after chemically induced colitis. AAT significantly decreased intestinal permeability in vitro and in vivo as part of a protective mechanism for both acute and chronic models of IBD. Conclusions: Our findings describe a beneficial role for AAT in IBD models through suppression of cytokine production and enhanced intestinal barrier function. This raises the possibility that AAT supplementation, which has a long history of proven safety, may have a therapeutic effect in human IBD.

Published
2013

30. Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis

Author

Aherne, Carol M., Collins, Colm B., Masterson, Joanne C., Tizzano, Marco, Boyle, Theresa A., Westrich, Joseph A., Parnes, Jason A., Furuta, Glenn T., Rivera-Nieves, Jesus, Eltzschig, Holger K., Aherne, Carol M., Collins, Colm B., Masterson, Joanne C., Tizzano, Marco, Boyle, Theresa A., Westrich, Joseph A., Parnes, Jason A., Furuta, Glenn T., Rivera-Nieves, Jesus, and Eltzschig, Holger K.

Abstract

Background: Inflammatory bowel diseases, encompassing Crohn’s disease and ulcerative colitis, are characterised by persistent leucocyte tissue infiltration leading to perpetuation of an inappropriate inflammatory cascade. The neuronal guidance molecule netrin-1 has recently been implicated in the orchestration of leucocyte trafficking during acute inflammation. We therefore hypothesised that netrin-1 could modulate leucocyte infiltration and disease activity in a model of inflammatory bowel disease. Design: DSS-colitis was performed in mice with partial genetic netrin-1 deficiency (Ntn-1+/- mice) or wild-type mice treated with exogenous netrin-1 via osmotic pump to examine the role of endogenous and therapeutically administered netrin-1. These studies were supported by in vitro models of transepithelial migration and intestinal epithelial barrier function. Results: Consistent with our hypothesis, we observed induction of netrin-1 during intestinal inflammation in vitro or in mice exposed to experimental colitis. Moreover, mice with partial netrin-1 deficiency demonstrated an exacerbated course of DSS-colitis compared to littermate controls, with enhanced weight loss and colonic shortening. Conversely, mice treated with exogenous mouse netrin-1 experienced attenuated disease severity. Importantly, permeability studies and quantitative assessment of apoptosis reveal that netrin-1 signalling events do not alter mucosal permeability or intestinal epithelial cell apoptosis. In vivo studies of leucocyte transmigration demonstrate suppression of neutrophil trafficking as a key function mediated by endogenous or exogenously administered netrin-1. Finally, genetic studies implicate the A2B adenosine receptor in netrin-1-mediated protection during DSS-colitis. Conclusions: The present study identifies a previously unrecognised role for netrin-1 in attenuating experimental colitis through limitation of neutrophil trafficking.

Published
2012

31. A Novel Model of TH2-polarized Chronic Ileitis: The SAMP1 Mouse

Author

McNamee, Eóin N., Wermers, Joshua D., Masterson, Joanne C., Collins, Colm B., Lebsack, Matthew D.P., Fillon, Sophie A., Robinson, Zachary, Grenawalt, Joanna, Lee, James J., Jedlicka, Paul, Furuta, Glenn T., Rivera-Nieves, Jesus, McNamee, Eóin N., Wermers, Joshua D., Masterson, Joanne C., Collins, Colm B., Lebsack, Matthew D.P., Fillon, Sophie A., Robinson, Zachary, Grenawalt, Joanna, Lee, James J., Jedlicka, Paul, Furuta, Glenn T., and Rivera-Nieves, Jesus

Abstract

Background & Aims—SAMP1/Yit mice develop spontaneous, segmental, transmural ileitis recapitulating many features of Crohn’s disease (CD). The ileitic phenotype may have arisen during crosses of SAMP1 mice selected for the presence of skin lesions. We hereby describe that the original SAMP1 strain similarly develops ileitis. Our aim was to characterize the histopathological and immunological features of this model and assess its responsiveness to standard IBD therapy. Methods—The time course of histopathological features of ileitis was assessed. Immune compartments were characterized by flow cytometry. Ileal cytokine profiles and transcription factors were determined by real-time RT-PCR. Finally, response to corticosteroid therapy and its effect on immune compartments and cellularity was evaluated. Results—Histological features and time course of disease were conserved, compared to those reported in SAMP1/Yit strains, with similar expansion of CD19+, CD4+ and CD8+ effector (CD44highCD62Llow), and central memory lymphocytes (CD44highCD62Lhigh). However, different from SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial TH1 polarization followed by TH2-polarized profile accompanied by prominent eosinophilia during late disease. Lastly, corticosteroids attenuated ileitis resulting in decreased lymphocyte subsets and cellularity of compartments. Conclusions—Here we report that the ileitic phenotype of SAMP1-related strains was already present in the original SAMP1 strain. By contrast the cytokine profile within terminal ilea of SAMP1 is distinct from the mixed TH1/TH2 profile of SAMP1/YitFc mice during late disease, as it shows predominant TH2 polarization. Dissemination of these strains may advance our understanding of CD pathogenesis, which in 60% of patients involves the terminal ileum.

Published
2010

34. Alpha-1-antitrypsin Therapy Ameliorates Acute Colitis and Chronic Murine Ileitis

Author

Collins, Colm B., primary, Aherne, Carol M., additional, Ehrentraut, Stefan F., additional, Gerich, Mark E., additional, McNamee, Eóin N., additional, McManus, Martine C., additional, Lebsack, Matthew D.P., additional, Jedlicka, Paul, additional, Azam, Tania, additional, de Zoeten, Edwin F., additional, Dinarello, Charles A., additional, and Rivera-Nieves, Jesús, additional

Published
2013
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41. Novel model of TH2-polarized chronic ileitis: The SAMP1 mouse

Author

McNamee, Eoin N., primary, Wermers, Joshua D., additional, Masterson, Joanne C., additional, Collins, Colm B., additional, Lebsack, Matthew D.P., additional, Fillon, Sophie, additional, Robinson, Zachary D., additional, Grenawalt, Joanna, additional, Lee, James J., additional, Jedlicka, Paul, additional, Furuta, Glenn T., additional, and Rivera-Nieves, Jesçs, additional

Published
2010
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43. CD44 Deficiency Attenuates Chronic Murine Ileitis

Author

Collins, Colm B., primary, Ho, Johnson, additional, Wilson, Theodore E., additional, Wermers, Joshua D., additional, Tlaxca, José L., additional, Lawrence, Michael B., additional, Solga, Michael, additional, Lannigan, Joanne, additional, and Rivera–Nieves, Jesús, additional

Published
2008
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45. γδ T cells protect against LPS‐induced lung injury

Author

Wehrmann, Fabian, Lavelle, James C., Collins, Colm B., Tinega, Alex N., Thurman, Joshua M., Burnham, Ellen L., and Simonian, Philip L.

Abstract

IL4‐expressing γδ T cells decrease TNF‐α production by alveolar macrophages, reducing accumulation of M1 macrophages that promotes lung injury. γδ T lymphocytes are a unique T cell population with important anti‐inflammatory capabilities. Their role in acute lung injury, however, is poorly understood but may provide significant insight into lung‐protective mechanisms occurring after injury. In a murine model of lung injury, wild‐type C57BL/6 and TCRδ−/−mice were exposed to Escherichia coliLPS, followed by analysis of γδ T cell and macrophage subsets. In the absence of γδ T cells, TCRδ−/−mice developed increased inflammation and alveolar‐capillary leak compared with wild‐type C57BL/6 mice after LPS exposure that correlated with expansion of distinct macrophage populations. Classically activated M1 macrophages were increased in the lung of TCRδ−/−mice at d 1, 4, and 7 after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild‐type animals. In response to LPS, Vγ1 and Vγ7 γδ T cells were expanded in the lung and expressed IL‐4. Coculture experiments showed decreased expression of TNF‐α by resident alveolar macrophages in the presence of γδ T cells that was reversed in the presence of an anti‐IL‐4‐blocking antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1 macrophages, inflammation, and alveolar‐capillary leak. Therefore, one mechanism by which Vγ1 and Vγ7 γδ T cells protect against LPS‐induced lung injury is through IL‐4expression, which decreases TNF‐α production by resident alveolar macrophages, thus reducing accumulation of M1 macrophages, inflammation, and alveolar‐capillary leak.

Published
2016
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46. Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Tregbalance during Crohnˈs‐like murine ileitis

Author

McNamee, Eóin N., Masterson, Joanne C., Veny, Marisol, Collins, Colm B., Jedlicka, Paul, Byrne, Fergus R., Ng, Gordon Y., and Rivera‐Nieves, Jesús

Abstract

CCR7 orchestrates the development of TH1/TH17/Tregsubsets, and their retention and lymphatic egress in experimental Crohnˈs disease. The regulation of T cell and DC retention and lymphatic egress within and from the intestine is critical for intestinal immunosurveillance; however, the cellular processes that orchestrate this balance during IBD remain poorly defined. With the use of a mouse model of TNF‐driven Crohnˈs‐like ileitis (TNFΔARE), we examined the role of CCR7 in the control of intestinal T cell and DC retention/egress during experimental CD. We observed that the frequency of CCR7‐expressing TH1/TH17 effector lymphocytes increased during active disease in TNFΔAREmice and that ΔARE/CCR7−/−mice developed exacerbated ileitis and multiorgan inflammation, with a marked polarization and ileal retention of TH1 effector CD4+T cells. Furthermore, adoptive transfer of ΔARE/CCR7−/−effector CD4+into lymphopenic hosts resulted in ileo‐colitis, whereas those transferred with ΔARE/CCR7+/+CD4+T cells developed ileitis. ΔARE/CCR7−/−mice had an acellular draining MLN, decreased CD103+DC, and decreased expression of RALDH enzymes and of CD4+CD25+FoxP3+Tregs. Lastly, a mAb against CCR7 exacerbated ileitis in TNFΔAREmice, phenocopying the effects of congenital CCR7 deficiency. Our data underscore a critical role for the lymphoid chemokine receptor CCR7 in orchestrating immune cell traffic and TH1 versus TH17 bias during chronic murine ileitis.

Published
2015
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47. Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn's-like murine ileitis.

Author

Collins, Colm B., Aherne, Carol M., McNamee, Eóin N., Lebsack, Matthew D. P., Eltzschig, Holger, Jedlicka, Paul, and Rivera-Nieves, Jesús

Subjects
*MACROPHAGES, *PHENOTYPES, *T cells, *DENDRITIC cells, *NECROSIS, *CROHN'S disease, *CD80 antigen, *CD86 antigen
Abstract

Background Imprinting an effector or regulatory phenotype on naïve T cells requires education at induction sites by dendritic cells (DC). Objectives To analyse the effect of inflammation on the frequency of mononuclear phagocytes (MP) and the effect of altering their frequency by administration of Flt3-L in chronic ileitis. Methods Using a tumour necrosis factor (TNF) driven model of ileitis (ie, TNFΔARE) that recapitulates many features of Crohn's disease (CD), dynamic changes in the frequency and functional state of MP within the inflamed ileum were assessed by flow cytometry, immunofluorescence and real-time reverse-transcription PCR and by generating CX3CR1 GFP-reporter TNFDARE mice. The effect of Flt3-L supplementation on the severity of ileitis, and the frequency of CD103+ DC and of FoxP3+ regulatory T cells was also studied in TNFΔARE mice. Results CD11cHi/MHCII+ MP accumulated in inflamed ilea, predominantly mediated by expansion of the CX3CR1+ MP subpopulation. This coincided with a decreased pro-regulatory CD103+ DC. The phenotype of these MP was that of activated cells, as they expressed increased CD80 and CD86 on their surface. Flt3-ligand administration resulted in a preferential expansion of CD103+ DC that attenuated the severity of ileitis in 20-week-old TNFΔARE mice, mediated by increased CD4+/CD25+/FoxP3+ regulatory T cells. Conclusions Results support a role for Flt3-L as a potential therapeutic agent in Crohńs-like ileitis. INSET: Significance of this study. [ABSTRACT FROM AUTHOR]

Published
2012
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49. IFN-γ-Mediated Induction of an Apical IL-IO Receptor on Polarized Intestinal Epithelia.

Author

Kominsky, Douglas J., Campbell, Eric L., Ehrentraut, Stefan F., Wilson, Kelly E., Kelly, Caleb J., Glover, Louise E., Collins, Colm B., Bayless, Amanda J., Saeedi, Bejan, Dobrinskikh, Evgenia, Bowers, Brittelle E., MacManus, Christopher F., Müller, Werner, Colgan, Sean P., and Bruderll, Dunja

Subjects
*INTERLEUKIN receptors, *EPITHELIAL cells, *CYTOKINES, *INFLAMMATORY bowel diseases, *INTERLEUKIN-10, *LABORATORY mice, *COLITIS, *DISEASE susceptibility
Abstract

Cytokines secreted at sites of inflammation impact the onset, progression, and resolution of inflammation. In this article, we investigated potential proresolving mechanisms of IFN-y in models of inflammatory bowel disease. Guided by initial microarray analysis, in vitro studies revealed that IFN-y selectively induced the expression of IL-10R1 on intestinal epithelia. Further analysis revealed that IL-10R1 was expressed predominantly on the apical membrane of polarized epithelial cells. Receptor activation functionally induced canonical IL-10 target gene expression in epithelia, concomitant with enhanced barrier restitution. Furthermore, knockdown of IL-10R1 in intestinal epithelial cells results in impaired barrier function in vitro. Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and suppressor of cytokine signaling 3 were increased in the epithelium and coincided with increased tissue IFN-y and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-y was sufficient to drive expression of IL-10R1 in the colonic epithelium. Studies of dextran sodium sulfate colitis in intestinal epithelialspecific IL-10Rl-null mice revealed a remarkable increase in disease susceptibility associated with increased intestinal permeability. Together, these results provide novel insight into the crucial and underappreciated role of epithelial IL-10 signaling in the maintenance and restitution of epithelial barrier and of the temporal regulation of these pathways by IFN-y. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Priming lymphocyte responsiveness and differential T cell signaling in pediatric IBD patients with Cannabis use.

Author

Sanctuary MR, Hudacheck CL, Jones AJ, Murphy BV, Welsh N, Klawitter J, Hoffenberg EJ, and Collins CB

Abstract

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., Competing Interests: Conflict of Interest No conflict of interest exist regarding this manuscript

Published
2024
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