scholarly journals Expression of OX40 Gene and its Serum Levels in Neuromyelitis Optica Patients

2019 ◽  
Vol 10 (1) ◽  
pp. 62-67
Author(s):  
Parya Alidadiani ◽  
Nahid Eskandari ◽  
Vahid Shaygannejad ◽  
Arezou Dabiri ◽  
Mostafa Manian ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neuromyelitis Optica ◽  
Autoimmune Disorder ◽  
Transcript Level ◽  
Serum Levels ◽  
Healthy Controls ◽  
Protein Levels ◽  
Age Related ◽  
T Cell Survival

AbstractNeuromyelitis optica (NMO), also known as Devic’s disease, is an autoimmune disorder of the central nervous system (CNS) in which immune system cells and antibodies primarily attack the optic nerves and the spinal cord. OX40 (CD134) is a tumor necrosis factor (TNF)-receptor family member expressed primarily on activated CD4+ and CD8+ T-cells. In an autoimmune disease, OX40 is typically up-regulated at sites of inflammation, and increases in the number of peripheral CD4+ T-cells expressing OX40. OX40 and its ligand OX40L are key TNF members that augment T-cell expansion, cytokine production, and promote T-cell survival. The aim of this study was to evaluate and compare of OX40 gene expression and its serum levels in patients with NMO and healthy controls. Twenty sex-/age-matched healthy controls (HC) (median age = 32 years, 15 females/5 males) were engaged for the present study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays, respectively. The results indicated OX40 expression in patients was significantly lower than in healthy controls (p = 0.001). However, the serum level of OX40 was not significantly different between groups (p = 0.37). In addition, the results indicated that CD134 expression was not age-related (p = 0.041). Overall, this study suggests to us that OX40 levels are not a suitable marker for diagnosis or treatment of NMO.

scholarly journals Alterations of Specific Lymphocytic Subsets with Aging and Age-Related Metabolic and Cardiovascular Diseases

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 246
Author(s):  
Ying Jen Chen ◽  
Yi Jen Liao ◽  
Van Thi Ngoc Tram ◽  
Chung Hao Lin ◽  
Kuo Chen Liao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cardiovascular Diseases ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Replicative Senescence ◽  
Cell Subset ◽  
Serum Levels ◽  
T Cell Subsets ◽  
Age Related

To investigate the association of immunosenescence with aged-related morbidity in the elderly, a clinical study was conducted to analyze and compare the alterations in peripheral blood (PB) T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, and age-matched elderly patients with metabolic diseases (E-MDs), with cardiovascular diseases (E-CVDs) or with both (E-MDs/E-CVDs). The frequencies of CD3T, CD8T and invariant natural killer T (iNKT) cells were decreased in the EH, E-MD and E-CVD cohorts, indicating a decline in defense function. Although CD4T and regulatory T (Treg) cell frequencies tended to increase with aging, they were lower in patients with E-MDs and E-CVDs. Subset analyses of T-cells consistently showed the accumulation of senescent T-cell in aging and in patients with E-MDs and E-CVDs, compared with YH volunteers. These accumulated senescent T-cells were undergoing apoptosis upon stimulation due to the replicative senescence stage of T-cells. In addition, serum levels of cytokines, including interferon (IF)-γ, transforming growth factor (TGF)-β and growth differentiation factor (GDF)-15, consistently reflected alterations in T-cell subsets. This study demonstrated that T-cell subset changes with paralleled alterations in cytokines were associated with aging and age-related pathogenesis. These altered T-cell subsets and/or cytokines can potentially serve as biomarkers for the prevention, diagnosis and treatment of age-related morbidities.

FOXP3-Positive Regulatory T-Cells in Acquired Aplastic Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2248-2248 ◽  
Author(s):  
Elena E. Solomou ◽  
Katayoun Rezvani ◽  
Stephan Mielke ◽  
Daniela Malide ◽  
Valeria Visconte ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Aplastic Anemia ◽  
Immunosuppressive Treatment ◽  
Foxp3 Expression ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Protein Levels ◽  
Immune Mediated

Abstract CD4+CD25+ regulatory T cells (Treg) have been hypothesized to control the development and progression of autoimmunity by suppressing autoreactive T cells. Treg are characterized by constitutive expression of membrane CD25 and intracellular expression of the transcription factor forkhead box (FOX) P3. FOXP3 and NF-AT1 have key roles in regulatory T-cell development and function: induction of FOXP3 in naïve T cells by gene transfer results in gain of a regulatory phenotype, and NF-AT1 modulates transcription of FOXP3. Treg display their suppressive properties on CD4+ CD25- T cells when activated via the T cell receptor or Toll-like receptor-2 (TLR2). Decreased numbers of FOXP3-positive regulatory Tregs have been associated with impaired immune homeostasis. Treg numbers are deficient in patients with active systemic lupus erythematosus, GVHD, and autoimmune hepatitis; in multiple sclerosis, decreased FOXP3 impairs Treg function. Acquired aplastic anemia (AA), the paradigm of immune mediated bone marrow failure syndromes, is characterized by immune-mediated destruction of hematopoietic stem cells. To examine expression of CD4+CD25+ T-cells in this disease, peripheral blood mononuclear cells from AA patients, sampled at diagnosis and prior to immunosuppressive therapy (n=18), were examined by flow cytometry: CD4+CD25hi+ T-cells were markedly reduced or absent in patients compared to healthy controls (n = 12, 0.08± 0.01 vs 0.4± 0.1%, p=0.001). CD4+CD25hi+FOXP3+ T-cells were also significantly lower in patients (0.05± 0.01 vs 0.32± 0.1, p=0.001). By immunoblot, we observed significantly decreased and often undetectable FOXP3 protein levels in CD4+CD25+ T cells from patients (n=8) compared to controls (n=6). Low FOXP3 protein levels correlated with decreased FOXP3 mRNA levels, as measured by RT-PCR and quantitative real-time PCR experiments (n=5, p=0.03). There were no differences in TLR2 in immunoblots between patients and healthy controls despite differences in FOXP3 expression. Patients (n=8) with low FOXP3 levels also showed decreased or absent NF-AT1 protein levels. These data collectively implicate a transcriptional mechanism for FOXP3 down-regulation. In confocal microscopy, purified CD4+CD25+ T cells from patients (n=5) showed undetectable NF-AT1 and FOXP3 levels as compared to controls (n=3). Four patients studied 3–6 months after first sampling and post-immunosuppressive treatment showed increased Tregs and FOXP3 expression; four further patients in complete remission after immunosuppressive treatment had increased CD4+CD25hi+ T-cells as compared to treatment-naïve patients. CD4+CD25+FOXP3+ regulatory T-cells are decreased in most patients with AA, probably through transcriptional regulation; decreased NFAT1 could explain low FOXP3 expression and Treg frequency. Treg employed as cellular therapy in a murine model of immune-mediated AA can prevent T cell-mediated marrow destruction (Chen J and Young NS, unpublished data). Treg defects are now implicated in autoimmune marrow failure in aplastic anemia.

scholarly journals AB0345 Th9 CELLS AND THEIR ASSOCIATED CYTOKINES: THE PROBABLE PLAYERS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND TYPE 1 DIABETES MELLITUS (T1DM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Clinical Manifestations ◽  
Moderate Activity ◽  
Healthy Controls ◽  
Group I ◽  
Pancreatic Islets Of Langerhans ◽  
Th9 Cells ◽  
Significant Difference

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared

scholarly journals AB0133 INCREASED SOLUBLE SEMAPHORIN 4D/CD100 IN THE PLASMA OF SJÖGREN’S SYNDROME AND ITS EFFECTS ON HUMAN SALIVARY GLAND CELL AND CD4+ T CELL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1367.1-1367
Author(s):  
S. E. Kang ◽  
S. U. Kim ◽  
R. H. Kim ◽  
H. J. Yoo ◽  
Y. J. Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Gland ◽  
T Cell ◽  
Tight Junction ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Human Salivary Gland ◽  
Semaphorin 4D ◽  
Aqp5 Expression ◽  
Ifn Γ

Background:Semaphorin 4D (SEMA4D) / CD100, known as a subfamily of axonal guidance proteins, has also been reported to act as an immunoregulator in several infectious and inflammatory diseases [1]. Sjögren’s syndrome (SS) is a systemic autoimmune disease that primarily affects the exocrine glands by infiltrated lymphocytes resulting in dryness of mouth and eyes. IL-17 was reported to impair the integrity of tight junction barrier and attenuate the expression of aquaporin 5 (AQP5), causing salivary gland dysfunction in SS [2].Objectives:This study was aimed to evaluate the role of SEMA4D in patients with SS and investigate the effect of SEMA4D on human salivary gland epithelial cell (SGEC) and T cell.Methods:Soluble SEMA4D levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) from patients with SS, non-SS sicca and healthy controls. Immortalized human SGECs, originated from acini (NS-SV-AC) and duct (NS-SV-DC), were used to evaluate the effects of SEMA4D. CD4+T cells from human peripheral blood were isolated to determine the secretion of cytokines in response to SEMA4D. IFN-γ and IL-17 were used to determine the effects on AQP5 expression of SGEC.Results:The levels of soluble SEMA4D in plasma were increased in patients with SS (median [interquartile range]: 1221.3 [393.5] pg/mL) compared to non-SS sicca (940.2 [355.1] pg/mL,p= 0.006) or healthy controls (909.5 [108.0] pg/mL,p <0.0001). The levels of soluble SEMA4D in plasma were correlated with the levels of several autoantibodies including anti-SSA (Spearman’s rho = 0.358,p= 0.006), anti-SSB (rho = 0.350,p= 0.007), and anti-muscarinic receptor 3 (M3R) Ab (rho = 0.495,p< 0.001), and also correlated with total IgG (rho = 0.431,p= 0.002). SEMA4D-stimulated SGECs showed decreased expression of tight junctions such as occludin and Zo-1. CD4+T cells secreted IFN-γ (p= 0.025), IL-17 (p= 0.028), and IL-21 (p= 0.007) with SEMA4D stimulation. IFN-γ and IL-17 decreased AQP5 expression in SGECs.Conclusion:SEMA4D contributed to decreased expression of tight junction in SGECs. SEMA4D induced production of IFN-γ and IL-17 in CD4+T cells and these cytokine decreased AQP5 expression in SGECs.References:[1]Worzfeld T, Offermanns S. Nat Rev Drug Discov. 2014;13(8):603-21.[2]Bhattarai KR, Junjappa R, Handigund M, Kim HR, Chae HJ. Autoimmun Rev. 2018;17(4):376-90.Disclosure of Interests:None declared

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

scholarly journals Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice

2016 ◽  
Vol 113 (5) ◽  
pp. 1333-1338 ◽  
Author(s):  
Kylie M. Quinn ◽  
Sophie G. Zaloumis ◽  
Tania Cukalac ◽  
Wan-Ting Kan ◽  
Xavier Y. X. Sng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A ◽  
Cytotoxic T Lymphocyte ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
Advanced Age ◽  
Age Related ◽  
Self Recognition ◽  
Underlying Mechanisms

In advanced age, decreased CD8+ cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naïve CTL precursors (CTLp). Although the age-related fall in CD8+ T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naïve CD8+ T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8+ T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naïve C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8+ T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, nonrandom alterations in TCR usage were observed, along with elevated CD5 and CD8 coreceptor expression. Collectively, these data demonstrate that naïve CD8+ T cells expressing markers of heightened self-recognition are selectively retained, but not clonally expanded, during aging.

scholarly journals MiR-410 Down-Regulates the Expression of Interleukin-10 by Targeting STAT3 in the Pathogenesis of Systemic Lupus Erythematosus

2016 ◽  
Vol 39 (1) ◽  
pp. 303-315 ◽  
Author(s):  
Dongmei Liu ◽  
Na Zhang ◽  
Xiaomei Zhang ◽  
Muting Qin ◽  
Youdan Dong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Autoimmune Disorder ◽  
Interleukin 10 ◽  
Luciferase Assay ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Targeting Effect

Background/Aims: Systemic lupus erythematosus (SLE) is a heterogeneous chronic inflammatory autoimmune disorder, in the pathogenesis of which miRNAs play a versatile function. The purpose of this study was to investigate the effect of miRNA-410 on the pathogenesis of SLE in T cells of SLE patients. Methods: Real-time PCR was used to test the mRNA levels of miRNA-410 in SLE patients and healthy controls. ELISA analysis was performed to examine the production levels of IL-10. Luciferase Assay was used to confirm the targeting effect of miRNA-410 on 3'UTR of STAT3 mRNA. Results: We found that the expression level of miR-410 in T cells of SLE patients was decreased comparing to that in healthy controls, whereas overexpression of miR-410 significantly reduced the expression levels of IL-10. Furthermore, miR-410 suppresses the transcription activity of STAT3 by binding directly to the 3 'UTR of STAT3 mRNA. Moreover, silence of STAT3 down regulated IL-10 expression in CD3+ T cells. Conclusion: Our results demonstrate that miR-410 is the key regulatory factor in the pathogenesis of SLE by regulating the expression of IL-10 through targeting STAT3. These data suggest a novel function of miR-410 and bring new insight into understanding the complex mechanisms involved in SLE.

Discussion On The Mechanism of Que In The Treatment of Breast Neoplasms And Immune Prevention And Treatment

2021 ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Xinqin Xiao ◽  
Guijuan Zhang ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Breast Neoplasms ◽  
Signaling Pathway ◽  
Immune Regulation ◽  
Γδ T Cells ◽  
Protein Levels ◽  
Stat1 Signaling ◽  
Mcf 7

Abstract Background: The precancerous disease of breast cancer is an inevitable stage in the emergence and development of breast neoplasms. Breast cancer (BC) is a common malignant tumor in female worldwide. A large number of literatures have proved that, as antitumor drugs, flavonoid compounds can promote proliferation and immune regulation of T cell. Many researchers believe that Quercetin (Que) has great potential in the field of anti-breast cancer. Besides that, γδ T cells are a class of non-traditional T cells, which have long attracted attention due to their potential in immunotherapy. Above all, JAK/STAT1 signaling pathway is closely related to the immunity.MethodsIn the experiment designed in this paper, we first used Que, one of the flavonoids, to screen the target gene. Then, MCF-10A, MCF-10AT, MCF-7 and MDA-MB231 BC cells were co-cultured with Que for 24h and 48h, apoptosis was found in some the cells. We then cultured Que with γδ T cells and found that Que can promote the proliferation of Vδ2 T cell subsets of γδ T cells, thus enhancing the killing effect of γδ T cells. Western blot was use to showed the change of JAK/STAT1 signaling pathway related proteins after the Que was co-cultured with MCF-10AT and MCF-7 for 48h.ResultsNetwork pharmacology has shown that Que related pathways include the JAK/STAT1 signaling pathway and are associated with precancerous breast cancers. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 in a time and concentration-dependent manner. Most importantly, Que can promote the differentiation of γδ T cells into the Vδ2 T cell subpopulation, this means that Que and γδ T cells may play a synergistic role in killing tumor cells and cellular immune regulation. In addition, our results showed that Que can increase in protein levels of IFNγ-R, p-JAK2 and p-STAT1, while the concomitant decrease protein levels of PD-L1.ConclusionsIn conclusion, Que plays a synergistic role in killing BC cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1, and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of BC.

scholarly journals VitaminD3 Regulates T Cell Immune Responses in Allergen and Rhinovirus Induced Asthma

2021 ◽  
Author(s):  
Susetta Finotto ◽  
Patricia Haag ◽  
Darja Andreev ◽  
Nina Li ◽  
Alexander Kiefer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Murine Model ◽  
Peripheral Blood ◽  
Serum Levels ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Asthmatic Children ◽  
Rhinovirus Infection

Abstract Background: Serum 25(OH)-Vitamin D3 (VitD3) deficiency during infancy has been associated with asthma. The potential therapeutic role of VitD3 given in the airways and its interference with the allergen and Rhinovirus was the objective of this study. Methods: In two cohorts of children with and without asthma, serum levels of the C-reactive protein (CRP) were correlated to Serum VitD3 and in peripheral blood T cell inhibitor marker Programmed cell death protein 1 (PD1) mRNA was analyzed. In a murine model, VitD3 was given intranasally in vivo and in vitro to lung cells with allergen and Rhinovirus. Results: In the cohorts of pre-school age children without (control) asthma, CRP and VitD3 levels inversely correlated. In preschool asthmatic children that did not receive VitD3 supplementation as infant had more episode of asthma exacerbation associated with high CRP serum level. In peripheral blood cells from control but not asthmatic children with higher serum levels of VitD3 had lower PD1 mRNA levels. In murine model, OVA intranasal challenge induced Innate Lymphoid Cells type 2 (ILC2)-associated markers and Eosinophils in BALF and VitD3 inhibited lung inflammation and ILC2 markers. Furthermore, VitD3 given intranasally, induced CD4+T cells and reduced PD1, T regulatory cells in the lung. Similarly, VitD3 had a suppressive role on CD4+PD1+ T cells involved in T cell exhaustion in the airways in the absence of ST2 after Rhinovirus infection. Conclusion: These data support an inhibitory role of VitD3 on T cell exhaustion after allergen and rhinovirus infection that is relevant for pediatric asthma.

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