Downregulation of B regulatory cells and upregulation of T helper 1 cells in children with Gaucher disease undergoing enzyme replacement therapy

Zahran, Asmaa M; Youssef, Mohamed Ahmed; Shafik, Engy A; Zahran, Zeinab Albadry M.; El‐Badawy, Omnia; Elgheet, Amir M Abo; Elsayh, Khalid I

doi:10.1007/s12026-020-09129-5

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…T lymphocytes are derived from bone marrow pluripotent stem cells. According to different functions in the immune response, T cells can be divided into several subgroups, such as helper T cells (Ths or CD4 + cells), regulatory T cells (Tregs), effector T cells (Tes), cytotoxic T cells (Tcs or CD8 + cells) and memory T cells (Tms) [129,130]. Plasma-derived EXOs from HNSCC patients contained TGF-β, OX40 (CD134), OX40L(CD134L), and HSP70.…”

Section: The Effects Of Tumour-derived Evs On Immune Cellsmentioning

confidence: 99%

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma

Guo

et al. 2021

J Exp Clin Cancer Res

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Head and neck squamous cell carcinoma (HNSCC) is one of the main malignant tumours affecting human health, mainly due to delayed diagnosis and high invasiveness. Extracellular vehicles (EVs) are membranous vesicles released by cells into the extracellular matrix that carry important signalling molecules and stably and widely exist in various body fluids, such as plasma, saliva, cerebrospinal fluid, breast milk, urine, semen, lymphatic fluid, synovial fluid, amniotic fluid, and sputum. EVs transport almost all types of bioactive molecules (DNA, mRNAs, microRNAs (miRNAs), proteins, metabolites, and even pharmacological compounds). These “cargoes” can act on recipient cells, reshaping the surrounding microenvironment and altering distant targets, ultimately affecting their biological behaviour. The extensive exploration of EVs has deepened our comprehensive understanding of HNSCC biology. In this review, we not only summarized the effect of HNSCC-derived EVs on the tumour microenvironment but also described the role of microenvironment-derived EVs in HNSCC and discussed how the “mutual dialogue” between the tumour and microenvironment mediates the growth, metastasis, angiogenesis, immune escape, and drug resistance of tumours. Finally, the clinical application of EVS in HNSCC was assessed.

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Section: The Effects Of Tumour-derived Evs On Immune Cellsmentioning

confidence: 99%

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma

Guo

et al. 2021

J Exp Clin Cancer Res

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“…Excess tissue amounts of GC, IFNγ, and their downstream effects have been reported in mouse models and human patients with GD [ 5 , 6 , 13 , 15 , 16 , 17 , 41 , 42 , 43 , 44 , 45 , 47 , 71 ]. Additionally, genetic deficiency of C5aR1 resulted in decreased tissue levels of GC, IFNγ, CXCL9–11, and reductions in tissue recruitment of T cell subsets in mouse models of GD [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…CD8 + T cells are important for inducing autoimmune and the anti-cancer and anti-viral responses [ 37 , 38 , 39 , 40 ]. T cell defects, T cell lymphomas, and increased incidence of CD3 + , CD4 + , CD8 + , CD3 + HLA-DR + , CD4 + HLA-DR + , and CD8 + HLA-DR + subset of activated T cells have been observed in lung and peripheral blood of patients with GD [ 41 , 42 , 43 , 44 , 45 , 46 ]. Significantly elevated levels of CD4 + T cells and modest changes in CD8 + T cells were present in liver, lung, spleen, and thymus of Gba1 9V/− mice [ 5 , 6 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

“…IFNγ drives increased expression of CXCR3 and its ligands, (e.g., CXCL9–11) that are increased in several inflammatory diseases [ 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Elevated levels of IFNγ and CXCL9–11 as well as increased numbers of tissue T cells were found in GD mouse models and human patients with GD [ 5 , 6 , 15 , 41 , 42 , 43 , 44 , 45 , 47 , 71 ]. However, the cellular mechanism(s) that causes increased tissue recruitment of T cells in Gba1 9V/− mice is unclear.…”

Section: Introductionmentioning

confidence: 99%

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C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease

Magnusen

Rani

McKay

et al. 2021

IJMS

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Gaucher disease is a lysosomal storage disease, which happens due to mutations in GBA1/Gba1 that encodes the enzyme termed as lysosomal acid β-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells. For example, augmented infiltration of T cells contributes to the increased production of pro-inflammatory cytokines, (e.g., IFNγ, TNFα, IL6, IL12p40, IL12p70, IL23, and IL17A/F). This leads to tissue damage in a genetic mouse model (Gba19V/−) of Gaucher disease. The cellular mechanism(s) by which increased tissue infiltration of T cells occurs in this disease is not fully understood. Here, we delineate role of the CXCR3 receptor and its exogenous C-X-C motif chemokine ligand 9 (CXCL9) in induction of increased tissue recruitment of CD4+ T and CD8+ T cells in Gaucher disease. Intracellular FACS staining of macrophages (Mϕs) and dendritic cells (DCs) from Gba19V/− mice showed elevated production of CXCL9. Purified CD4+ T cells and the CD8+ T cells from Gba19V/− mice showed increased expression of CXCR3. Ex vivo and in vivo chemotaxis experiments showed CXCL9 involvement in the recruitment of Gba19V/− T cells. Furthermore, antibody blockade of the CXCL9 receptor (CXCR3) on T cells caused marked reduction in CXCL9- mediated chemotaxis of T cells in Gba19V/− mice. These data implicate abnormalities of the CXCL9-CXCR3 axis leading to enhanced tissue recruitment of T cells in Gaucher disease. Such results provide a rationale for blockade of the CXCL9/CXCR3 axis as potential new therapeutic targets for the treatment of inflammation in Gaucher disease.

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“…Так, на выборке из 20 пациентов с БГ показано увеличение доли цитотоксических Т-клеток и снижение NK-клеток по сравнению со здоровыми людьми, данный факт авторы связывают с участием данных популяций в патогенезе и прогрессировании БГ [13]. Помимо этого, показано, что, несмотря на ФЗТ, Т-хелперы и B-регуляторные клетки у пациентов с БГ значительно снижены по сравнению с контрольной группой [14]. Показано также значительное снижение доли регуляторных Т-лимфоцитов и их функциональной активности у детей с БГ [12].…”

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Age-related changes in the parameters of cellular immunity, the activity of intracellular lymphocyte dehydrogenases and functional activity of neutrophils in children with Gaucher disease

Kurbatova,

Movsisyan,

Konyashin

et al. 2024

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Gaucher disease (GD) is an autosomal recessively inherited disease that belongs to the group of lysosomal storage diseases. In GD, there is chronic activation of the macrophage system, disruption of the regulatory functions of macrophages, a shift in cytokine regulation towards pro-inflammatory cytokines and the development of chronic inflammation involving all immune cells, which can lead to changes in the composition of both major and minor populations of lymphocytes. Reduced beta-glucocerebrosidase activity impairs normal lysosomal function and autophagy, leading to the intracellular accumulation of glycosphingolipids, creating a self-sustaining cycle of impaired glucocerebroside utilization with the aggravation of both lysosomal and mitochondrial functions. It is known that untreated patients with GD are susceptible to more frequent and complicated infectious diseases, which presumably may arise due to changes in the functional activity of neutrophils caused by the disruption of the process of phagocytosis and oxidative burst in this cell population. The aim: to study the age-related features of the composition of the major and minor populations of peripheral blood lymphocytes, the activity of intracellular dehydrogenases of lymphocytes and the functional activity of neutrophils in children with GD. The study was approved by the Independent Ethics Committee and the Scientific Council of the National Medical Research Center for Children's Health of Ministry of Healthcare of the Russian Federation. The study included 73 children with GD, of which 26 children were examined at different age periods (1 child – 4 tests, 3 children – 3 tests, 22 children – 2 tests), the comparison group consisted of 148 healthy children comparable in age. The determination of the subpopulation composition of lymphocytes, the study of succinate dehydrogenase activity in the major and minor populations of lymphocytes (by immunocytochemical method) and the assessment of the functional activity of neutrophils were carried out using flow cytometry. The parameters of lymphocyte subpopulations were analyzed as percentage deviations from the age norm. The activity of intracellular dehydrogenases (succinate dehydrogenase, NADH dehydrogenase, lactate dehydrogenase) was determined by a cytomorphodensitometric method using image analysis. The statistical calculations were performed using the Statistica 10.0 program (StatSoft, USA). A decrease in NK cells and an increase in Th17 cells and activated T helper cells are usually observed in children with GD with age. The analysis of the activity of intracellular dehydrogenases revealed a decrease in the processes of oxidative phosphorylation and glycolysis in peripheral blood lymphocytes in children with GD. The functional activity of neutrophils in the majority of children with GD corresponded to the reference values.

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Downregulation of B regulatory cells and upregulation of T helper 1 cells in children with Gaucher disease undergoing enzyme replacement therapy

Cited by 5 publications

References 37 publications

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma

The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease

Age-related changes in the parameters of cellular immunity, the activity of intracellular lymphocyte dehydrogenases and functional activity of neutrophils in children with Gaucher disease

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