CD4+CD45RA−FOXP3lowRegulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

Silva-Neta, Helena L.; Castro, Maria Carolina Accioly Brelaz de; Chagas, Mardonny B. O.; Mariz, Henrique Ataíde; Arruda, Rodrigo Gomes de; Vasconcelos, Viviane Ferreira de; Pereira, Michelly Cristiny; Romano, Audrey; Pitta, Ivan R.; Marques, Cláudia Diniz Lopes; Duarte, Ângela Luzia Branco Pinto; Rego, MJ; Pitta, M. G. R.

doi:10.1155/2018/3419565

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Autoimmune diseases also result from the imbalance of immune homeostasis. The alternatively spliced CD45RO isoform has been found to be increased in systemic lupus erythematosus (SLE), and CD45 isoforms have been suggested as biomarkers of SLE and are capable of distinguishing the functional status of T lymphocytes [ 58 ]. Several meta-analyses of genome-wide association screens on multiple sclerosis (MS) patients, and healthy controls, demonstrated significant association of single nucleotide polymorphisms correlated with CD6 alternative splicing and MS [ 59 , 60 , 61 ].…”

Section: Abnormally Spliced Isoforms In Immune-associated Diseasesmentioning

confidence: 99%

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Huang

2021

Genes

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The human immune response is a complex process that responds to numerous exogenous antigens in preventing infection by microorganisms, as well as to endogenous components in the surveillance of tumors and autoimmune diseases, and a great number of molecules are necessary to carry the functional complexity of immune activity. Alternative splicing of pre-mRNA plays an important role in immune cell development and regulation of immune activity through yielding diverse transcriptional isoforms to supplement the function of limited genes associated with the immune reaction. In addition, multiple factors have been identified as being involved in the control of alternative splicing at the cis, trans, or co-transcriptional level, and the aberrant splicing of RNA leads to the abnormal modulation of immune activity in infections, immune diseases, and tumors. In this review, we summarize the recent discoveries on the generation of immune-associated alternative splice variants, clinical disorders, and possible regulatory mechanisms. We also discuss the immune responses to the neoantigens produced by alternative splicing, and finally, we issue some alternative splicing and immunity correlated questions based on our knowledge.

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Section: Abnormally Spliced Isoforms In Immune-associated Diseasesmentioning

confidence: 99%

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Huang

2021

Genes

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“…1). Nonsuppressive FOXP3 + T cells produce proinflammatory cytokines (e.g., IL 17) and may therefore promote inflammation and autoimmunity (24,40,41), but the immunological function of this Treg subpopulation is largely unknown.…”

Section: Assessment Of Cd4 + Treg Subsetsmentioning

confidence: 99%

Maternal and Cord Blood 25-Hydroxyvitamin D3 Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study

Thorsen

Collier

Pezic

et al. 2021

The Journal of Immunology

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and the Barwon Infant Study Investigator Group 1Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal sampling frame, 158 mother-infant pairs had data on the following: 1) 25-hydroxyvitamin D 3 (25(OH)D 3 ) measures in both maternal peripheral blood (28-to 32-wk gestation) and infant CB; 2) proportions (percentage of CD4 + T cells) of CB Treg subsets (CD4 + CD45RA + FOXP3 low naive Treg, and CD4 + CD45RA 2 FOXP3 high activated Treg [aTreg]); and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D 3 was 85.4 and 50.7 nmol/l for maternal and CB samples, respectively. Higher maternal 25(OH)D 3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5%; 95% confidence interval [CI]: 1-9%), and aTreg (AMD per 25 nmol/l increase: 17%; 95% CI: 6-28%). Furthermore, a positive association between CB 25(OH)D 3 levels and CB aTreg (AMD per 25 nmol/l increase: 29%; 95% CI: 13-48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D 3, may play a role in the adaptive neonatal immune system via induction of FOXP3 + Tregs. Further studies of immune priming actions of antenatal 25(OH)D 3 are warranted.

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“…In addition, we and others have observed a significant increase in Fr.III cells within CD4 + T cells of patients with active SLE compared with values found in healthy controls (HCs) . Finally, this subtype of T cells has been reported as a potential biomarker of disease activity in SLE Brazilian patients . However, it is currently unknown why Fr.III cells increase in SLE patients, and the detailed function of these cells in the pathogenic development of SLE needs further investigation.…”

Section: Introductionmentioning

confidence: 97%

BACH2 regulates the function of human CD4⁺CD45RA⁻Foxp3^l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

Zheng

Huang

et al. 2019

Eur J Immunol

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Although CD4+CD45RA−Foxp3l° cytokine‐secreting T cells (Fr.III cells) have been reported to be increased in systemic lupus erythematosus (SLE), their function and effects on response of B cells are still unclear. Here, we dissect how BACH2 regulates Fr.III cells function and promotes B‐cell response in active SLE patients. We measured cytokines and BACH2 expression, and found that Fr.III cells from SLE patients produce much more inflammatory cytokines and were more able to promote B‐ cell proliferation, IgG, IgA, and TNF‐α production than controls in a co‐culture system. Fr.III cells expressed high levels of ICOS and CD154, but a low level of Tfr and BACH2, BACH2 expression was negatively correlated with SLE Disease Activity Index. Overexpressed of BACH2 in Fr.III cells, decreased cytokines expression and reduced B‐cell response. Furthermore, we identified a reduction of H3K27ac level binding at the BACH2 locus in the SLE Fr.III cells and SLE serum stimulation decreased H3K27ac binding at the BACH2 locus, which could be restored using trichostatin A (TSA). In conclusion, BACH2 was associated with SLE disease activity, regulated the function of Fr.III cells, and promoted B‐cells response. Targeting BACH2 may be a new immune intervention therapy of SLE.

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CD4⁺CD45RA⁻FOXP3^lowRegulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

Cited by 10 publications

References 39 publications

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Maternal and Cord Blood 25-Hydroxyvitamin D3 Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study

BACH2 regulates the function of human CD4⁺CD45RA⁻Foxp3^l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

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CD4+CD45RA−FOXP3lowRegulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

Cited by 10 publications

References 39 publications

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Maternal and Cord Blood 25-Hydroxyvitamin D3 Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study

BACH2 regulates the function of human CD4+CD45RA−Foxp3l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus

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CD4⁺CD45RA⁻FOXP3^lowRegulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

BACH2 regulates the function of human CD4⁺CD45RA⁻Foxp3^l° cytokine‐secreting T cells and promotes B‐cell response in systemic lupus erythematosus