scholarly journals Vitamin D receptor expression in SLE peripheral blood CD4+T cells is associated with disease activity and cell apoptosis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Lingying Niu ◽  
Fan Wang ◽  
Xiaojun Tang ◽  
Chun Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Disease Activity ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Activity Index ◽  
Receptor Expression ◽  
Th2 Cells ◽  
Tfh Cells

ABSTRACT Objectives Systemic lupus erythematosus (SLE) is characterised by accumulated cell apoptosis. Vitamin D receptor (VDR) has immunomodulatory effect and potent anti-apoptosis activities. The aim of this study was to examine the correlation between CD4+T cells VDR expression, cell apoptosis, and disease activity in patients with SLE. Methods Forty-five SLE patients were recruited and 50 healthy individuals served as controls. The expression of VDR in CD4+T cells and their subsets were determined by flow cytometry. The correlations between VDR expression and cell apoptosis or disease parameters in SLE patients were analysed. Results VDR expression in CD4+T cells and their subsets were upregulated in SLE patients, especially in help T (Th)1, regulatory T (Treg), and follicular helper T (Tfh) cells. Frequency of VDR-positive CD4+T cells was positively associated with SLE disease activity index (SLEDAI)-2K values and inversely correlated with serum C3 concentration. The frequency of VDR-positive CD4+T cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, and Tfh cells was positively correlated with cells apoptosis. Conclusion VDR expression in CD4+T cells and their subsets were increased in SLE. VDR expression was positively associated with disease activity and cell apoptosis in SLE patients.

Higher Frequency of Peripheral Blood Interleukin 21 Positive Follicular Helper T Cells in Patients with Ankylosing Spondylitis

2013 ◽  
Vol 40 (12) ◽  
pp. 2029-2037 ◽  
Author(s):  
Fei Xiao ◽  
Hai-Yu Zhang ◽  
Yi-Jun Liu ◽  
Ding Zhao ◽  
Yu-Xing Shan ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Activity Index ◽  
Disease Activity Index ◽  
Inducible Costimulator ◽  
Before And After ◽  
Interleukin 21

Objective.The role of follicular Th (TFH) cells remains unclear in the pathogenesis of ankylosing spondylitis (AS). Our study examined the frequency of different subsets of circulating CXCR5+CD4+ T cells in patients with AS before and after receiving therapy.Methods.Percentages of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and interleukin 21 (IL-21)+ CXCR5+CD4+ T cells in 26 patients with AS and 12 healthy controls (HC) were examined by flow cytometry, and the disease activity of individual patients was measured by Bath AS Disease Activity Index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM, and C-reactive protein (CRP) were examined and the values of erythrocyte sedimentation rate (ESR) were measured. The potential association among these measures was analyzed.Results.In comparison with that in HC, significantly increased percentages of CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but not CXCR5+CD4+ICOS+ and PD-1+ICOS+CXCR5+CD4+ T cells, and elevated concentrations of serum IL-21 were detected in patients with AS (p = 0.001, p = 0.012, p < 0.001, p = 0.233, p = 0.216, p < 0.001, respectively). Treatment with meloxicam, thalidomide, and etanercept for 1 month significantly reduced percentages of IL-21+CXCR5+CD4+ T cells and concentrations of serum IL-21 (p < 0.001, p < 0.001, respectively), accompanied by significantly minimized disease activity in drug responders, but not in the drug nonresponders. Further, percentages of IL-21+CXCR5+CD4+ T cells were positively correlated with BASDAI in patients (r = 0.6, p = 0.0012) and in the drug-responders 1 month after treatment (r = 0.68, p = 0.005), while the percentages of PD-1+CXCR5+CD4+ T cells were negatively correlated with BASDAI (r = −0.58, p = 0.0018).Conclusion.These data suggest that IL-21+CXCR5+CD4+ T cells may be associated with development of AS and that the frequency of IL-21+CXCR5+CD4+ T cells may be a biomarker for evaluation of disease activity and drug responses in patients with AS, particularly in drug-responding patients.

scholarly journals IL-4–producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells

2009 ◽  
Vol 206 (5) ◽  
pp. 1001-1007 ◽  
Author(s):  
Irah L. King ◽  
Markus Mohrs
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Cd4 T Cells ◽  
Helminth Infection ◽  
Th2 Cells ◽  
Mesenteric Lymph Nodes ◽  
Th2 Response ◽  
Tfh Cells ◽  
Follicular Helper

Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4+ T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4–mediated link between Th2 cells and B lymphocytes, the location of IL-4–producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4–competent Th2 cells are found throughout the B and T cell areas, IL-4–producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.

scholarly journals T follicular helper cells differentiate from Th2 cells in response to helminth antigens

2009 ◽  
Vol 206 (5) ◽  
pp. 991-999 ◽  
Author(s):  
Arielle Glatman Zaretsky ◽  
Justin J. Taylor ◽  
Irah L. King ◽  
Fraser A. Marshall ◽  
Markus Mohrs ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Th2 Cells ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Th2 Cell ◽  
Reporter Mice ◽  
Relationship Of ◽  
The Relationship

The relationship of T follicular helper (TFH) cells to other T helper (Th) subsets is controversial. We find that after helminth infection, or immunization with helminth antigens, reactive lymphoid organs of 4get IL-4/GFP reporter mice contain populations of IL-4/GFP-expressing CD4+ T cells that display the TFH markers CXCR5, PD-1, and ICOS. These TFH cells express the canonical TFH markers BCL6 and IL-21, but also GATA3, the master regulator of Th2 cell differentiation. Consistent with a relationship between Th2 and TFH cells, IL-4 protein production, reported by expression of huCD2 in IL-4 dual reporter (4get/KN2) mice, was a robust marker of TFH cells in LNs responding to helminth antigens. Moreover, the majority of huCD2/IL-4–producing Th cells were found within B cell follicles, consistent with their definition as TFH cells. TFH cell development after immunization failed to occur in mice lacking B cells or CD154. The relationship of TFH cells to the Th2 lineage was confirmed when TFH cells were found to develop from CXCR5− PD-1− IL-4/GFP+ CD4+ T cells after their transfer into naive mice and antigen challenge in vivo.

scholarly journals Vitamin D Up-Regulates the Vitamin D Receptor by Protecting It from Proteasomal Degradation in Human CD4+ T Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96695 ◽  
Author(s):  
Martin Kongsbak ◽  
Marina R. von Essen ◽  
Lasse Boding ◽  
Trine B. Levring ◽  
Peter Schjerling ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Vitamin D Receptor ◽  
Cd4 T Cells ◽  
Proteasomal Degradation

scholarly journals Elocalcitol Inhibits Inflammatory Responses in Human Thyroid Cells and T Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3626-3634 ◽  
Author(s):  
E. Borgogni ◽  
E. Sarchielli ◽  
M. Sottili ◽  
V. Santarlasci ◽  
L. Cosmi ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Vitamin D Receptor ◽  
Cd4 T Cells ◽  
Inflammatory Responses ◽  
Cytokine Secretion ◽  
Human Thyroid ◽  
Cell Mediated Immunity ◽  
Th2 Response ◽  
Thyroid Cells

T-helper 1 (Th1) cell-mediated inflammatory responses predominate in the early pathogenesis of Graves’ disease (GD), whereas Th2 cell-mediated immunity may play a role in later stages. The chemokine CXCL10 and its receptor CXCR3 are expressed in most thyroid glands of early GD patients. Circulating CXCL10 levels inversely correlate with disease duration; CXCL10 maximal expression also correlates with interferon (IFN)γ levels in recent GD onset. Methimazole (MMI) reduces CXCL10 secretion by isolated thyrocytes, decreases serum CXCL10 levels, and promotes a transition from Th1 to Th2 dominance in patients in GD active phase. Vitamin D receptor agonists exhibit antiinflammatory properties and promote tolerance induction. We investigated the effects and the mechanism of action of a nonhypercalcemic vitamin D receptor agonist, elocalcitol (BXL-628), compared with MMI on CXCL10 secretion induced by proinflammatory cytokines. Furthermore, we studied the effects of both drugs on Th1, Th17, and Th2 cytokine secretion in CD4+ T cells. ELISA, cytometry, immunocytochemistry, Western blot, and quantitative real-time PCR were used for protein and gene analysis. In human thyrocytes, elocalcitol inhibited IFNγ and TNFα-induced CXCL10 protein secretion more potently than MMI. Elocalcitol impaired both cytokine intracellular pathways, whereas MMI was effective only on the IFNγ pathway. In CD4+ T cells, elocalcitol decreased Th1- and Th17-type cytokines, and promoted Th2-type cytokine secretion. Elocalcitol and MMI inhibited Th1 cytokine-mediated responses in thyrocytes and CD4+ T cells. In addition, elocalcitol promoted a shift toward a Th2 response. In conclusion, elocalcitol could represent a novel pharmacological tool in the treatment of autoimmune thyroid diseases.

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