Aberrant histone modification and inflammatory cytokine production of peripheral CD4+ T cells in patients with oral lichen planus

The pathogenesis of preeclampsia (PreE) involves the failure of the maternal immune system to normally tolerate the pregnancy. Inflammatory cytokines are elevated in PreE-affected women with a concurrent decrease in anti-inflammatory cytokine production. Consistent with what other groups have observed in mouse models of hypertension during pregnancy and in human PreE-affected pregnancies, we observed increased inflammatory cytokine production and CD4+ T helper populations in our chronic infusion of vasopressin (AVP) mouse model of PreE. The mechanisms of immune modulation by AVP have not been elucidated. As increased T cell activity is involved in the development of PreE, the objective of this study was to investigate if CD4+ T cells express AVP receptors. Splenic CD4+ T cells were negatively purified from C57BL/6J saline and AVP-infused (24 ng/hour) dams. Expression of AVP receptors (AVPR) 1a, 1b, 2, and the aminopeptidase LNPEP (catalyzes AVP degradation) was determined via qPCR. Raw cycle threshold (Ct) values were normalized (ΔCt) against the 18S rRNA endogenous control. Mouse CD4+ T cells express all AVP receptors and LNPEP. By ANOVA, AVPR2 is the highest expressed receptor in CD4+ T cells from saline (N=7, p=0.002) and AVP-infused (N=10, p<0.0001) dams. Human maternal mononuclear cells, obtained from the University of Iowa Maternal-Fetal Tissue Bank (IRB #200910784) from control and PreE-affected women, were similarly analyzed. As in mouse CD4+ T cells, human control (N=27, p<0.0001) and PreE-affected (N=26, p<0.0001) CD4+ T cells most highly expressed AVPR2. AVPR1a was also highly expressed while AVPR1b was the least expressed. CD4+ T cells isolated from human PreE-affected women expressed significantly lower AVPR1a (10.0±0.3 N=27 vs. 11.1±0.2 N=0.23, p=0.009) and increased LNPEP (17.2±0.5 N=27 vs. 15.1±0.3 N=26, p=0.001) than controls. Here, we demonstrate CD4+ T cells, both mouse and human, express AVP receptors and that 1a and 2 are highest expressed. Although the actions of AVP on the vasculature are primarily mediated through AVPR1a, these data suggest AVP may differentially act through AVPR1a to mediate immune responses during PreE.

Download Full-text

MiR-29b interacts with IFN-γ and induces DNA hypomethylation in CD4+ T cells of oral lichen planus

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2019.09.252 ◽

2020 ◽

Vol 147 ◽

pp. 1248-1254 ◽

Cited By ~ 1

Author(s):

Jing Zhang ◽

Guan-Ying Chen ◽

Fang Wang ◽

Gang Zhou

Keyword(s):

T Cells ◽

Lichen Planus ◽

Cd4 T Cells ◽

Oral Lichen Planus ◽

Dna Hypomethylation ◽

Ifn Γ ◽

Oral Lichen

Download Full-text

Decreased MIR-425 Induced Inflammatory Cytokine Production via N-RAS Upregulation in CD4+ T Cells of Primary Biliar Cholangitis

Journal of Hepatology ◽

10.1016/s0168-8278(16)01199-5 ◽

2016 ◽

Vol 64 (2) ◽

pp. S643-S644

Author(s):

R. Nakagawa ◽

R. Muroyama ◽

K. Koike ◽

C. Saeki ◽

S. Ito ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Inflammatory Cytokine Production

Download Full-text

TLR4-induced B7-H1 on keratinocytes negatively regulates CD4+T cells and CD8+T cells responses in oral lichen planus

Experimental Dermatology ◽

10.1111/exd.13244 ◽

2017 ◽

Vol 26 (5) ◽

pp. 409-415 ◽

Cited By ~ 5

Author(s):

Jing Zhang ◽

Ya-qin Tan ◽

Ming-hui Wei ◽

Xiao-jing Ye ◽

Guan-ying Chen ◽

...

Keyword(s):

T Cells ◽

Lichen Planus ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Oral Lichen Planus ◽

Oral Lichen

Download Full-text

Different Expression of MicroRNA-146a in Peripheral Blood CD4+ T Cells and Lesions of Oral Lichen Planus

Inflammation ◽

10.1007/s10753-016-0316-4 ◽

2016 ◽

Vol 39 (2) ◽

pp. 860-866 ◽

Cited By ~ 12

Author(s):

Jian-Guang Yang ◽

Ya-Ru Sun ◽

Guan-Ying Chen ◽

Xue-Yi Liang ◽

Jing Zhang ◽

...

Keyword(s):

T Cells ◽

Lichen Planus ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Oral Lichen Planus ◽

Oral Lichen

Download Full-text

Deregulation of circ_003912 contributes to pathogenesis of erosive oral lichen planus by via sponging microRNA-123, -647 and -31 and upregulating FOXP3

Molecular Medicine ◽

10.1186/s10020-021-00382-4 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Zhen Huang ◽

Fen Liu ◽

Wenjuan Wang ◽

Shaobo Ouyang ◽

Ting Sang ◽

...

Keyword(s):

T Cells ◽

Lichen Planus ◽

Inflammatory Cytokines ◽

Cd4 T Cells ◽

Oral Lichen Planus ◽

Molecular Mechanisms ◽

Treg Cells ◽

Foxp3 Mrna ◽

Ifn Γ ◽

Oral Lichen

Abstract Background The FOXP3/miR-146a/NF-κB axis was previously reported to modulate the induction and function of CD4+ Treg cells to alleviate oral lichen planus. Also, other signaling pathways including microRNA-155-IFN-γ loop and FOXP3/miR-146a/TRAF6 pathways were reported to be involved in the pathogenesis of oral lichen planus. In this study, we aimed to investigate the molecular mechanism underlying the pathogenesis of EOLP. Method CircRNA microarray was used to observe the expression of candidate circRNAs in CD4+ T-cells collected from different groups. Real-time PCR and Western blot were conducted to observe the changes in the expression of different miRNAs, mRNAs and proteins. Flow cytometry was performed to compare the counts of Treg cells in the HC and EOLP groups, and ELISA was performed to evaluate the changes in the expression of inflammatory cytokines. Result No obvious differences were seen between the HC and EOLP groups in terms of age and gender. Among all candidate circRNAs, the expression of circ_003912 was most dramatically elevated in CD4+ T-cells collected from the EOLP group. The levels of miR-1231, miR-31, miR-647, FOXP3 mRNA and miR-146a were decreased while the expression of TRAF6 mRNA was increased in CD4+ T-cells collected from the EOLP group. The count of Treg cells in the EOLP group was dramatically increased. The levels of inflammatory cytokines including IL-4 IFN-γ, IL-10 and IL-2 were influenced by the presence of circ_003912. In CD4+ T-cells in the EOLP group, the levels of IL-4 and IL-10 were decreased while the levels of IFN-γ and IL-2 were increased. The presence of miR-1231, miR-31 and miR-647 all obviously inhibited the expression of circ_003912, which was validated to sponge the expression of above miRNAs. Also, FOXP3 mRNA was proved to be targeted by miR-1231, miR-31 and miR-647. Transfection of circ_003912 up-regulated the expression of circ_003912, miR-146a and FOXP3 mRNA/protein while down-regulating the expression of miR-1231, miR-31, miR-647, and TRAF6 mRNA/protein. The levels of inflammatory cytokines including IL-4 IFN-γ, IL-10 and IL-2 as well as the speed of cell proliferation were influenced by circ_003912. Conclusion In this study, we investigated the molecular mechanisms underlying the pathogenesis of EOLP which involved the functioning of circ_003912. We first demonstrated that circ_003912 was up-regulated in CD4+ T-cells of the EOLP group. And miRNAs including miR-1231, miR-31 and miR-647 were sponged by circ_003912 and down-regulated in CD4+ T cells of the EOLP group, which subsequently up-regulated the expression of FOXP3 and miR-146a, and resulted in the inhibition of NF-kB.

Download Full-text