Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell–Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction

Jamwal, Deepa R.; Marati, Raji V; Harrison, Christy A.; Midura-Kiela, Monica T.; Paz, Vanessa Ribeiro Figliuolo da; Besselsen, David G.; Kiela, Pawel R.

doi:10.1093/ibd/izz191

Cited by 8 publications

(7 citation statements)

References 48 publications

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“…Although CD8 + T cells build a protective barrier against attack by surrounding host cells, their proliferation indicates that numerous pathogens are attacking. Accumulating evidence suggests that colitis is characterised by an expansion of colonic CD8 + T cells [ 66 – 68 ]. Distinct from the increase in CD8 + T cells in Y-DSS pigs, CD8 + T cells remained at steady-state levels in M-DSS pigs, but an increase in CD4 + T cells was observed.…”

Section: Discussionmentioning

confidence: 99%

Host-microbiota interaction-mediated resistance to inflammatory bowel disease in pigs

et al. 2022

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Background Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human health. Microbiota plays an essential role in regulating immunity and autoimmunity in the host organism, but the influence of host-microbiota interactions on disease resistance phenotypes remains unclear. Here, multiomics analysis was performed to identify potential regulatory mechanisms of disease resistance at both the microbiome and host levels in two pig breeds. Results Acute colitis models were established in Min pigs and Yorkshire pigs, and control and diseased individuals were compared. Compared with Yorkshire pigs under the same nutritional and management conditions, Min pigs exhibited strong disease resistance, as indicated by a low disease activity index (DAI) and a low histological activity index (HAI). Microbiota sequencing analysis showed that potentially harmful microbes Desulfovibrio, Bacteroides and Streptococcus were enriched in diseased individuals of the two breeds. Notably, potentially beneficial microbes, such as Lactobacillus, Clostridia and Eubacterium, and several genera belonging to Ruminococcaceae and Christensenellaceae were enriched in diseased Min pigs and were found to be positively associated with the microbial metabolites related to intestinal barrier function. Specifically, the concentrations of indole derivatives and short-chain fatty acids were increased in diseased Min pigs, suggesting beneficial action in protecting intestinal barrier. In addition, lower concentrations of bile acid metabolites and short-chain fatty acids were observed in diseased Yorkshire pigs, which were associated with increased potentially harmful microbes, such as Bilophila and Alistipes. Concerning enrichment of the immune response, the increase in CD4+ T cells in the lamina propria improved supervision of the host immunity response in diseased Min pigs, contributing to the maintenance of Th2-type immune superiority and immune tolerance patterns and control of excessive inflammation with the help of potentially beneficial microbes. In diseased Yorkshire pigs, more terms belonging to biological processes of immunity were enriched, including Toll-like receptors signalling, NF-κB signalling and Th1 and Th17-type immune responses, along with the increases of potentially harmful microbes and damaged intestinal barrier. Conclusions Cumulatively, the results for the two pig breeds highlight that host-microbiota crosstalk promotes a disease resistance phenotype in three ways: by maintaining partial PRR nonactivation, maintaining Th2-type immune superiority and immunological tolerance patterns and recovering gut barrier function to protect against colonic diseases.

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Section: Discussionmentioning

confidence: 99%

Host-microbiota interaction-mediated resistance to inflammatory bowel disease in pigs

et al. 2022

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“…CD3 + T cell is one of the subsets in the splenic leukocytes, accounting for one-fourth of all splenocytes [ 34 , 41 ]. Studies show that dysfunction of CD3 + mediates gut inflammation with higher Il6 and Il1b levels, while anti-CD3 antibody remarkably decreases inflammatory phenotype by inhibiting the production and secretion of proinflammatory cytokine [ 42 , 43 ]. Furthermore, we also found that the population of CD4 + T cells was reduced in the colon tissue from Npr1 −/− and DSS mice.…”

Section: Discussionmentioning

confidence: 99%

Null Function of Npr1 Disturbs Immune Response in Colonic Inflammation During Early Postnatal Stage

et al. 2022

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Natriuretic peptide receptor 1 (NPR1) is conventionally known as a regulator of vascular homeostasis. Here, we generated an Npr1 knockout mouse model with CRISPR/Cas9 technology and found that homozygous mice (Npr1−/−) exhibited weight loss and poor survival rate during early postnatal stage. Careful examination revealed unexpectedly that Npr1−/− mice developed colitis characterized by shortened colon, evident colonic mucosal damage, increased histopathological score, and higher colonic expression of proinflammatory cytokines interleukin-1B (IL1B) and -6 (IL6). RNA-sequencing analysis revealed that differentially expressed genes were prominently enriched in the biological pathways related to immune response in both spleen and colon of Npr1−/− mice. Cytofluorimetric analysis demonstrated that leukocytes in the spleen were significantly increased, particularly, the populations of neutrophil and CD3+ T cell were elevated but CD4+ T cells were decreased in Npr1−/− mice. Administration of 8-Br-cGMP, a downstream activator of NPR1, restored these immune-cell populations disturbed in Npr1−/− mice and lessened the colitis-related phenotypes. To validate the involvement of Npr1 in colitis, we examined another mouse model induced by dextran sodium sulfate (DSS) and found a decreased Npr1 expression and shifted immune-cell populations as well. Importantly, 8-Br-cGMP treatment exhibited a similar effect in the restoration of immune-cell populations and attenuation of colonic inflammation in DSS mice. Our data indicate that loss of Npr1 possibly interrupts immune response, which is critical to the pathogenesis of colitis in the early life.

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“…CD is short for leukocyte differentiation antigen, CD3 is a class of antigens on the surface of T lymphocytes, and CD3+ refers to mature T lymphocytes. CD3 binds to the T cell receptor and can transmit antigen signals to T lymphocytes ( 26 , 27 ). CD4+ lymphocytes, namely helper T cells, have the function of assisting humoral and cellular immunity ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Remifentanil combined with dexmedetomidine on the analgesic effect of breast cancer patients undergoing modified radical mastectomy and the influence of perioperative T lymphocyte subsets

2022

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ObjectiveTo study the analgesic effect of breast cancer patients undergoing modified radical mastectomy (MRM) and the influence of perioperative T lymphocyte subsets by remifentanil combined with dexmedetomidine.Methods80 breast patients were divided into control group and research group based on the anesthesia protocol. Patients in control group was given remifentanil for anesthesia induction and maintenance, and patients in research group was given remifentanil and dexmedetomidine for anesthesia induction and maintenance. We compared the anesthesia time, operation time, surgical blood loss, postoperative wake-up time, extubation time, incidence of adverse reactions, VAS score and T lymphocyte subsets in peripheral blood in the two groups of patients.ResultsThe baseline data including age, height, weight and BMI, ASA classification, stage of breast cancer, frequency of neoadjuvant therapy, and surgical characteristics including anesthesia time, operation time and bleeding volume all have no significant difference between two groups (P > 0.05). Compared to control group, the time of wake up and extubation in patients of research group were all significantly decreased (P < 0.05), and significantly decreased MBP and HR after loading dose of dexmedetomidine in research group (P < 0.05). The VAS scores of patients at 4, 8, 12, 16, 20 and 24 h after surgery in the research group are all significantly lower than those in the control group (P < 0.05). Before induction of anesthesia, there was no significant difference in the ratio of CD4+, CD8+ and CD4+/CD8+ T lymphocytes in peripheral blood between the two groups (P > 0.05). At 1 h during operation and 24 h after operation, the ratio of CD4+ and CD4+/CD8+ cells in the research group was significantly higher than these of the control group (P < 0.05), while the ratio of CD8+ cells was lower than that of the control group (P < 0.05).ConclusionFor breast cancer patients undergoing MRM, the use of remifentanil combined with dexmedetomidine can enhance postoperative analgesia and reduce postoperative immunosuppression.

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Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell–Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction

Cited by 8 publications

References 48 publications

Host-microbiota interaction-mediated resistance to inflammatory bowel disease in pigs

Host-microbiota interaction-mediated resistance to inflammatory bowel disease in pigs

Null Function of Npr1 Disturbs Immune Response in Colonic Inflammation During Early Postnatal Stage

Remifentanil combined with dexmedetomidine on the analgesic effect of breast cancer patients undergoing modified radical mastectomy and the influence of perioperative T lymphocyte subsets

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