T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

Ko, Haeun; Kim, Chan Johng; Im, Sungbin

doi:10.3389/fimmu.2022.866549

Cited by 17 publications

(13 citation statements)

References 71 publications

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“…There is evidence that a negative feedback between Th1-type and Th2-type immune responses regulates normal immune balance. In SLE patients, an influx of Th2 cells inhibits the release of Th1 cells, thus supporting the hypothesis that the immune disorder of “Th2 dominance” is responsible for SLE ( Ko et al, 2022 ).…”

Section: Discussionsupporting

confidence: 69%

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Xiang

Zhang²,

Zhang³

et al. 2022

Front. Pharmacol.

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Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE.Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16.Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs.Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

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Section: Discussionsupporting

confidence: 69%

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Xiang

Zhang²,

Zhang³

et al. 2022

Front. Pharmacol.

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“…It has also been explored for treating autoimmune disorders like discoid lupus erythematosus 51. It has also been reported that Th2-associated immunity may play an essential role in a subset patients with SLE,52 echoing our discovery that IL-4 abolishes B ND anergy and contributes to the generation of self-reactive immune responses.…”

Section: Discussionmentioning

confidence: 97%

Interleukin 4-driven reversal of self-reactive B cell anergy contributes to the pathogenesis of systemic lupus erythematosus

et al. 2023

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ObjectivesReactivation of anergic autoreactive B cells (BNDcells) is a key aetiological process in systemic lupus erythematosus (SLE), yet the underlying mechanism remains largely elusive. This study aimed to investigate how BNDcells participate in the pathogenesis of SLE and the underlying mechanism.MethodsA combination of phenotypical, large-scale transcriptome and B cell receptor (BCR) repertoire profiling were employed at molecular and single cell level on samples from healthy donors and patients with SLE. Isolated naïve B cells from human periphery blood were treated with anti-CD79b mAb in vitro to induce anergy. IgM internalisation was tracked by confocal microscopy and was qualified by flow cytometer.ResultsWe characterised the decrease and disruption of BNDcells in SLE patients and demonstrated IL-4 as an important cytokine to drive such pathological changes. We then elucidated that IL-4 reversed B cell anergy by promoting BCR recycling to the cell surface via STAT6 signalling.ConclusionsWe demonstrated the significance of IL-4 in reversing B cell anergy and established the scientific rationale to treat SLE via blocking IL-4 signalling, also providing diagnostic and prognostic biomarkers to identify patients who are most likely going to benefit from such treatments.

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“…Furthermore, tumor-specific Th2 cells were also reported to eradicate tumors by triggering an in situ inflammatory immune response [34]. Additionally, the interplay between Th1 and Th2 responses is crucial for maintaining immune balance and preventing pathological conditions [35]. IL-9, mainly produced by Th9 cells, can escalate immune responses by stimulating the production of other pro-inflammatory cytokines (such as IL-4, IL-5 and IL-13), and promote the activity of mast cells, CD8 + T cells, and natural killer (NK) cells.…”

Section: Discussionmentioning

confidence: 99%

LRRK2G2019S mutation suppresses differentiation of Th9 and Treg cells via JAK/STAT3

Zheng,

Jaffery,

Guerrero

et al. 2024

Preprint

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The Leucine-rich repeat kinase-2 (LRRK2) G2019S mutation, resulting in aberrantly enhanced kinase activity, is one of the well-recognized genetic risk factors in Parkinson’s Disease (PD). Increased LRRK2 activity was also observed in immune cells from PD patients. Emerging results have also unveiled an upsurge in α-synuclein (α-syn)-specific CD4+T cell responses in PD patients. Given thatLRRK2mutations in PD are germline mutations, there are unmet meets to explore whetherLRRK2G2019S mutation contributes to the pathogenesis of PD via altering CD4+T-cell functions. To fill this knowledge gap, we generated a new T cell receptor (TCR) transgenic mouse strain bearingLRRK2G2019S knock-in mutation, OT-II/LRRK2 (Refer to Mut). As CD4+T cells from OT-II mice specifically recognize ovalbumin, this new strain enables us to explore the impact ofLRRK2G2019S mutation on T-cell functions in an antigen-specific manner. We found that the abundance and proliferation of major immune subsets in spleen tissue from Mut mice are comparable to wild-type (OT-II, Refer to WT) control. However, when we characterized T cell differentiation in these two strains, T cells derived from Mut mice displayed increased Th2 differentiation (IL-4) and decreased Th9 (IL-9) and Treg (Foxp3+%) differentiation.LRRK2G2019S mutation significantly altered the expression levels of master transcription factors (TFs) for T cell differentiation. Specifically, Mut T cells displayed an increase in mRNA expression ofGata3(TF for Th2), a decrease in expression ofIrf4andFoxp3(TFs for Th9 and Treg, respectively). Mechanistically,LRRK2mutation decreased IL-9 production and Treg cell population through the JAK/STAT3 signaling. In conclusion, LRRK2 plays a critical role in regulating T cell differentiation, warranting further studies to evaluate the impacts of altered T cell differentiation led byLRRK2mutation in dopaminergic neuron damages.

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T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

Cited by 17 publications

References 71 publications

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Interleukin 4-driven reversal of self-reactive B cell anergy contributes to the pathogenesis of systemic lupus erythematosus

LRRK2G2019S mutation suppresses differentiation of Th9 and Treg cells via JAK/STAT3

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