Faculty Opinions recommendation of Interleukin-23 drives intestinal inflammation through direct activity on T cells.

Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RBlo separates T effector/memory (Tem) cells from naive (CD44−CD45RBhi) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4+Foxp3+ regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.

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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice

Journal of Visualized Experiments ◽

10.3791/63293 ◽

2021 ◽

Author(s):

Wenjing Yang ◽

Tianming Yu ◽

Yingzi Cong

Keyword(s):

T Cells ◽

Adoptive Transfer ◽

Intestinal Inflammation ◽

Immunodeficient Mice

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Aberrant expression of interleukin-23-regulated miRNAs in T cells from patients with ankylosing spondylitis

Arthritis Research & Therapy ◽

10.1186/s13075-018-1754-1 ◽

2018 ◽

Vol 20 (1) ◽

Cited By ~ 9

Author(s):

Ning-Sheng Lai ◽

Hui-Chun Yu ◽

Chien-Hsueh Tung ◽

Kuang-Yung Huang ◽

Hsien-Bin Huang ◽

...

Keyword(s):

T Cells ◽

Ankylosing Spondylitis ◽

Aberrant Expression ◽

Interleukin 23

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TRPM2 Is Not Required for T-Cell Activation and Differentiation

Frontiers in Immunology ◽

10.3389/fimmu.2021.778916 ◽

2022 ◽

Vol 12 ◽

Author(s):

Niels C. Lory ◽

Mikolaj Nawrocki ◽

Martina Corazza ◽

Joanna Schmid ◽

Valéa Schumacher ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Transient Receptor Potential ◽

Cell Function ◽

Intestinal Inflammation ◽

Activation Markers

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+ signal that is crucial for T-cell function. The Ca2+ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+ through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived from in vitro studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+ signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulation in vitro, Trpm2-/- and WT CD4+ and CD8+ T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of Trpm2-/- CD8+ T cells and unimpaired differentiation of CD4+ T cells into Th1, Th17, and Treg cells under specific polarizing conditions. In vivo, Trpm2-/- and WT CD8+ T cells showed equal specific responses to Listeria monocytogenes after infection of WT and Trpm2-/- mice and after transfer of WT and Trpm2-/- CD8+ T cells into infected recipients. CD4+ T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT and Trpm2-/- CD4+ T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.

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Do mucosal T cells prevent intestinal inflammation?

Gastroenterology ◽

10.1016/s0016-5085(00)70186-7 ◽

2000 ◽

Vol 118 (5) ◽

pp. 974-977 ◽

Cited By ~ 14

Author(s):

Mitchell Kronenberg ◽

Hilde Cheroutre

Keyword(s):

T Cells ◽

Intestinal Inflammation ◽

Mucosal T Cells

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Cloning and Expression of the Tibetan Pig Interleukin-23 Gene and Its Promotion of Immunity of Pigs to PCV2 Vaccine

Vaccines ◽

10.3390/vaccines8020250 ◽

2020 ◽

Vol 8 (2) ◽

pp. 250

Author(s):

Yongle Xiao ◽

Huan Zhang ◽

Jianlin Chen ◽

Yi Chen ◽

Jinghai Li ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Mononuclear Cells ◽

B Cell Lymphoma ◽

Cloning And Expression ◽

Porcine Circovirus ◽

Peripheral Blood Mononuclear ◽

Pcv2 Vaccine ◽

Interleukin 23

Vaccines against Porcine circovirus type 2 (PCV2) have been studied intensely and found to be effective in decreasing mortality and improving growth in swine populations. In this study, interleukin-23 (IL-23) gene was cloned from peripheral blood mononuclear cells (PBMCs) of Tibetan pigs and inserted into a eukaryotic VR1020 expression vector-VRIL23. Coated with chitosan (CS), the VRIL23-CS was intramuscularly injected into 3-week-old piglets with PCV2 vaccine. The blood was collected after vaccination at 0, 1, 2, 4, 8, and 12 weeks, respectively, to detect the immunological changes. The IgG2a and specific PCV2 antibodies were detected using ELISA, and blood CD4+ and CD8+ T cells were quantified by flow cytometry. Quantitative fluorescence PCR was used to evaluate the expression of immune genes. The results indicate that leukocytes, erythrocytes, and CD4+ and CD8+ T cells increased significantly in the blood of VRIL23-CS inoculated piglets in comparison with the control (p < 0.05) and so did the IgG2a and PCV2 antibodies. In addition, the expressions of Toll-like receptor (TLR) 2, TLR7, cluster of differentiation (CD) 45, IL-15, IL-12, signal transducer and activator of transcription (STAT)1, STAT2, STAT3, STAT4, and B-cell lymphoma (Bcl)-2 genes were also obviously higher in the VRIL23-CS inoculated pigs at different time points (p < 0.05). Overall, the results demonstrated that VRIL23-CS can enhance the comprehensive immune responses to PCV2 vaccine in vivo and has the promising potential to be developed into a safe and effective adjuvant to promote the immunity of pig against PCV disease.

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LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis

Immunity ◽

10.1016/j.immuni.2018.07.007 ◽

2018 ◽

Vol 49 (2) ◽

pp. 342-352.e5 ◽

Cited By ~ 45

Author(s):

David Bauché ◽

Barbara Joyce-Shaikh ◽

Renu Jain ◽

Jeff Grein ◽

Karin S. Ku ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Lymphoid Cell ◽

Innate Lymphoid Cell ◽

Group 3 ◽

Interleukin 23

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Retinoic Acid Is Elevated in the Mucosa of Patients With Active Ulcerative Colitis and Displays a Proinflammatory Role by Augmenting IL-17 and IFNγ Production

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa121 ◽

2020 ◽

Vol 27 (1) ◽

pp. 74-83 ◽

Cited By ~ 3

Author(s):

Ritika Rampal ◽

Nahidul Wari ◽

Amit Kumar Singh ◽

Ujjwalkumar Das ◽

Sawan Bopanna ◽

...

Keyword(s):

Ulcerative Colitis ◽

T Cells ◽

Retinoic Acid ◽

Crucial Role ◽

Intestinal Inflammation ◽

Γδ T Cells ◽

Inflammatory Conditions ◽

Invariant T Cells ◽

Active Disease

Abstract Background All-trans retinoic acid (RA) plays a crucial role in promoting Foxp3+ Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN) γ and interleukin (IL)-17 differentiation in vitro. Methods In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFNγ, Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and γδ T cells) in patients with ulcerative colitis in remission or with active inflammation. Results This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFNγ in tissue CD4+, CD8+, mucosal associated invariant T+ cells, and γδ + T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL-17, IFNγ) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers.

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