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1.
J Immunol ; 208(12): 2866-2876, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35867673

RESUMO

Diffuse large B cell lymphoma comprises a heterogeneous group of B cell-derived tumors, with different degrees of aggressiveness, as defined by their cellular origin and tissue microenvironment. Using the spontaneous Bc.DLFL1 lymphoma originating from a BALB/c mouse as a diffuse large B cell lymphoma model, in this study we demonstrate that the lymphoma cells display surface phenotype, IgH V-region somatic mutations, transcription factor characteristics and in vivo location to splenic extrafollicular regions of age-associated B cells (ABCs), corresponding to T-bet+ and Blimp-1+/CD138- plasmablasts derivation. The expansion of lymphoma cells within lymphoid tissues took place in a close arrangement with CD11c+ dendritic cells, whereas the extranodal infiltration occurred selectively in the mesentery and omentum containing resident gp38/podoplanin+ fibroblastic reticular cells. Antagonizing BAFF-R activity by mBR3-Fc soluble receptor fusion protein led to a significant delay of disease progression. The extranodal expansion of Bc.DLFL1 lymphoma within the omental and mesenteric adipose tissues was coupled with a significant change of the tissue cytokine landscape, including both shared alterations and tissue-specific variations. Our findings indicate that while Bc.DLFL1 cells of ABC origin retain the positioning pattern within lymphoid tissues of their physiological counterpart, they also expand in non-lymphoid tissues in a BAFF-dependent manner, where they may alter the adipose tissue microenvironment to support their extranodal growth.


Assuntos
Linfoma Difuso de Grandes Células B , Animais , Linfócitos B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Mesentério/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microambiente Tumoral
2.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338701

RESUMO

The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.


Assuntos
Doenças Autoimunes , Doença de Hashimoto , Gravidez , Humanos , Feminino , Autoanticorpos , Gestantes , Proteínas de Choque Térmico , Proteínas de Choque Térmico HSP70 , Imunoglobulina G , Chaperonina 60 , Imunoglobulina M
3.
Apoptosis ; 25(9-10): 715-729, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32737651

RESUMO

Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10-6 M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4+ T cells. Activation of both extrinsic and intrinsic apoptotic pathways started after 2 h of DX treatment in CD4 SP thymocytes and was 3 × higher than in CD4+ splenocytes, while in Treg cells, weak activation of the extrinsic apoptotic pathway started only after 3 h. We also investigated the expression of 21 apoptosis-related molecules using a protein array and found higher level of both pro-and anti-apoptotic molecules in Tregs compared to CD4+ T cells. 4 h in vitro DX treatment induced upregulation of most apoptosis-related molecules both in Tregs and CD4+ T cells, except for the decrease of Bcl-2 expression in CD4+ T cells. We found high basal cytosolic Ca2+ levels in untreated Treg cells, which further increased after DX treatment, while the specific TCR-induced Ca2+ signal was lower in Tregs than in CD4+ T cells. Our results suggest that in the background of the relative apoptosis resistance of Treg cells to GCs might be their high basal cytosolic Ca2+ level and upregulated Bcl-2 expression. In contrast, downregulation of Bcl-2 expression in CD4+ T cells can explain their higher, DX-induced apoptosis sensitivity.


Assuntos
Glucocorticoides/farmacologia , Hormônios/farmacologia , Mitocôndrias/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Apoptose/genética , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Citocromos c/genética , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/metabolismo , Humanos , Camundongos , Mitocôndrias/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Timócitos/efeitos dos fármacos
4.
Acta Psychol (Amst) ; 241: 104080, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37976918

RESUMO

BACKGROUND: Studies have focused more on the outcome than on the antecedents of burnout. We aimed to develop a new measurement tool for burnout, including the antecedents and different components drawing from theories of the developmental aspect of burnout. METHODS: In this cross-sectional study we tested the Burnout Antecedents and Components Questionnaire on a convenience sample of teachers (n = 618, 83.9 % women; mean age 44.52 years). We used confirmatory factor analyses to test our measurement model. We examined the concurrent validity with the Maslach Burnout Inventory. We also tested construct validity with depression, overcommitment, demographic characteristics and work-related factors. RESULTS: The confirmatory factor analyses supported our measurement model with seven primary factors (need to prove oneself, overload of tasks, neglecting one's needs, conflict between values, interpersonal conflicts, passivity, and emotional drain) and three second-order factors (excessive effort, conflict, and total depletion). The covariates in the Maslach Burnout Inventory showed that emotional exhaustion had a strong relationship with the first- and second-order factors. Overcommitment showed a stronger relationship with factors at the beginning whereas depression showed a stronger relationship with factors at the end of the process. Demographic characteristics and work-related factors did not show strong associations. CONCLUSIONS: The Burnout Antecedents and Components Questionnaire is a promising measurement tool with good convergent validity. Future research should further validate our questionnaire for burnout research, prevention, and screening. It adds a new dimension to the measurement of burnout. The approach involving the antecedents in measuring burnout among teachers can guide future research and tailored prevention programs.


Assuntos
Esgotamento Profissional , Humanos , Feminino , Adulto , Masculino , Estudos Transversais , Hungria/epidemiologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/diagnóstico , Esgotamento Profissional/psicologia , Esgotamento Psicológico/epidemiologia , Inquéritos e Questionários
5.
Pharmaceuticals (Basel) ; 15(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35056114

RESUMO

Transient Receptor Potential Ankyrin 1 (TRPA1) has been reported to influence neuroinflammation and lymphocyte function. We analysed the immune phenotype and activation characteristics of TRPA1-deficient mice (knockout-KO) generated by targeted deletion of the pore-loop domain of the ion channel. We compared TRPA1 mRNA and protein expression in monocyte and lymphocyte subpopulations isolated from primary and secondary lymphatic organs of wild type (WT) and KO mice. qRT-PCR and flow cytometric studies indicated a higher level of TRPA1 in monocytes than in lymphocytes, but both were orders of magnitude lower than in sensory neurons. We found lower CD4+/CD8+ thymocyte ratios, diminished CD4/CD8 rates, and B cell numbers in the KO mice. Early activation marker CD69 was lower in CD4+ T cells of KO, while the level of CD8+/CD25+ cells was higher. In vitro TcR-mediated activation did not result in significant differences in CD69 level between WT and KO splenocytes, but lower cytokine (IL-1ß, IL-6, TNF-α, IL-17A, IL-22, and RANTES) secretion was observed in KO splenocytes. Basal intracellular Ca2+ level and TcR-induced Ca2+ signal in T lymphocytes did not differ significantly, but interestingly, imiquimod-induced Ca2+ level in KO thymocytes was higher. Our results support the role of TRPA1 in the regulation of activation, cytokine production, and T and B lymphocytes composition in mice.

6.
J Immunol Res ; 2021: 9953317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124274

RESUMO

PURPOSE: Decreased expression of TLR homolog CD180 in peripheral blood B cells and its potential role in antibody production have been described in autoimmune diseases. Effectiveness of anti-CD20 therapy in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) strengthens the role of B cells in the pathogenesis. Therefore, we aimed to investigate the CD180 expression of peripheral blood B cell subsets in NMOSD and MS patients and analyze the levels of natural anti-citrate synthase (CS) IgG autoantibodies and IgG antibodies induced by bacterial infections reported to play a role in the pathogenesis of NMOSD or MS. METHODS: We analyzed the distribution and CD180 expression of peripheral blood B cell subsets, defined by CD19/CD27/IgD staining, and measured anti-CS IgM/G natural autoantibody and antibacterial IgG serum levels in NMOSD, RRMS, and healthy controls (HC). RESULTS: We found decreased naïve and increased memory B cells in NMOSD compared to MS. Among the investigated four B cell subsets, CD180 expression was exclusively decreased in CD19+CD27+IgD+ nonswitched (NS) memory B cells in both NMOSD and MS compared to HC. Furthermore, the anti-CS IgM natural autoantibody serum level was lower in both NMOSD and MS. In addition, we found a tendency of higher anti-CS IgG natural autoantibody levels only in anti-Chlamydia IgG antibody-positive NMOSD and MS patients. CONCLUSIONS: Our results suggest that reduced CD180 expression of NS B cells could contribute to the deficient natural IgM autoantibody production in NMOSD and MS, whereas natural IgG autoantibody levels show an association with antibacterial antibodies.


Assuntos
Antígenos CD/metabolismo , Autoanticorpos/imunologia , Subpopulações de Linfócitos B/imunologia , Citrato (si)-Sintase/imunologia , Células B de Memória/imunologia , Esclerose Múltipla/imunologia , Neuromielite Óptica/imunologia , Adulto , Idoso , Antígenos CD/genética , Células Cultivadas , Regulação para Baixo , Feminino , Humanos , Imunoglobulina M/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Toll-Like/genética , Adulto Jovem
7.
Stress Health ; 33(5): 530-539, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28066969

RESUMO

This study validated the Hungarian version of the Maslach Burnout Inventory-Educators Survey on a sample of n = 211 elementary and secondary teachers. To test factorial validity, we ran a series of confirmatory analysis with eight models. The best fitting model was the bifactor model with general burnout and three specific factors: emotional exhaustion, depersonalization, and personal accomplishment. Analyzing the covariates revealed that gender and age were not associated with burnout, but depressive symptoms and overcommitment had a significant relationship with general burnout, and overcommitment was related to emotional exhaustion as well.


Assuntos
Esgotamento Profissional/psicologia , Depressão/psicologia , Psicometria/métodos , Professores Escolares/psicologia , Logro , Adulto , Esgotamento Profissional/epidemiologia , Despersonalização/epidemiologia , Despersonalização/psicologia , Depressão/epidemiologia , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Professores Escolares/estatística & dados numéricos
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