Multi-Source Pathways of T Follicular Helper Cell Differentiation

Ma, Xiaoxue; Nakayamada, Shingo

doi:10.3389/fimmu.2021.621105

Cited by 22 publications

(19 citation statements)

References 80 publications

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“…Additionally, our results demonstrated high levels of IL-2, IL-17 and IFN-g in plasma from SLE patients, particularly in active SLE patients, but plasma levels of TNF-a, IL-4, IL-10 and IL-12 were not different among HC and SLE patients, which was partly consistent with previous reports (19,33,34,37). Differentiated Tfh cells can also produce high levels of IL-2 that can negatively inhibit Tfh cell differentiation by activating the transcription factor STAT-5, which contributes to maintain the balance of Tfh cells in vivo (19,35). IL-12 can lead to Th1 and Tfh1 cell differentiation by regulating T-bet and Bcl-6 signals to secrete IFN-g and enhance antibody isotype class-switching (19,33).…”

Section: Discussionsupporting

confidence: 89%

“…Cytokine-skewed Tfh cells can regulate B differentiation, antibody production and Ig isotype class-witching, which play critical roles in the humoral immune response of autoimmune diseases including SLE (19,35). Conventional Tfh cell differentiation require IL-6 and IL-21,which induce naïve CD4 + T cells to differentiate into Tfh cells by activating STAT-3 and upregulating Bcl-6 (10,19).…”

Section: Discussionmentioning

confidence: 99%

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Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Jin

Chen²,

Wu³

et al. 2022

Front. Immunol.

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ObjectiveSystemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.MethodsThirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.ResultsFrequencies of CD4+CXCR5+CD45RA-effector cTfh cells, PD1+cTfh, PD1+ICOS+cTfh, PD1+cTfh1, PD1+cTfh2, PD1+cTfh17, and PD1+ICOS+cTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1+ICOS+ cTfh or PD1+ICOS+ cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1+ICOS+ Tfh cells expansion in both thymus and spleen of MRL/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-γ was increased in the peripheral blood of MRL/lpr mice.ConclusionTfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Jin

Chen²,

Wu³

et al. 2022

Front. Immunol.

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“…The TFH cell subsets are essential for inducing high-affinity antibodies ( 30 – 34 ). IL-4-secreting TFH-TH2 cells are known to contribute to humoral immunity ( 102 – 104 ), and interestingly, together with TFH-TH17 cells but not TFH-TH1 cells, they provide support to naive B cells to produce IgM, and for isotype switching to IgG and IgA ( 32 , 34 ). The frequency of circulating TFH have been shown to be correlated with neutralizing antibodies in viral infections such as HIV-1 ( 37 ), and now SARS-CoV-2 ( 25 , 28 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

T cell perturbations persist for at least 6 months following hospitalization for COVID-19

et al. 2022

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COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+ CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69+ CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

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“…Cytokines participate in the activation and derivation of immune cells, and thus are regarded as central to the immune system ( 36 ). Different cytokines exhibit diverse functions.…”

Section: Discussionmentioning

confidence: 99%

Effects of Glycyrrhiza Polysaccharides on Chickens' Intestinal Health and Homeostasis

Che

et al. 2022

Front. Vet. Sci.

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The overuse of antibiotics in poultry farming causes the accumulation of drug residue in animals' bodies and the occurrence of antibiotic-resistant bacteria, which not only compromise animals' health but ultimately endanger human health. Thus, there is an urgent need for a novel poultry feed additive to substitute for excessive antibiotics. Glycyrrhiza polysaccharides (GPS) derived from Chinese licorice have shown promising immunomodulatory effects in previous studies. The present study investigated the pharmacological effects of GPS on poultry intestines to assess whether it can be used as a feed additive. The results show that GPS can increase production of sIgA, promote the secretion activity of goblet cells, alter the gut microbial composition and lead to changes in short-chain fatty acids. GPS also elevated both Th1 and Th2 immune responses by facilitating the expression of IL-2, IL-4, IL-1β, and IFN-γ while increasing the proportion of both CD4+ and CD8+ cells in the intestine. Moreover, the results of 16S rRNA gene sequencing showed that GPS could significantly change intestinal microbiota composition in the intestine, evidenced by the increased proportion of Bacteroides, Butyricicoccus and Eisenbergiella, as well as a decreased portion of Erysipelatoclostridium, leading to a healthier intestinal microbiota composition for the host. Taken together, it can be concluded that GPS is safe to use as a novel feed additive that can be used as an alternative to prophylactic antibiotics in poultry feeding.

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Multi-Source Pathways of T Follicular Helper Cell Differentiation

Cited by 22 publications

References 80 publications

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

T cell perturbations persist for at least 6 months following hospitalization for COVID-19

Effects of Glycyrrhiza Polysaccharides on Chickens' Intestinal Health and Homeostasis

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