T cell receptor signaling in the differentiation and plasticity of CD4+ T cells

Meitei, Heikrujam Thoihen; Lal, Girdhari

doi:10.1016/j.cytogfr.2022.08.001

Cited by 16 publications

(14 citation statements)

References 235 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31,32 Through T cell receptor (TCR), naïve CD4 + T cells can pick up the matching antigens' molecular signals. 33,34 Naïve CD4 In conclusion, HCQ has the potential to be a promising therapeutic approach in the clinic for patients with autoimmune POI, as demonstrated by the fact that it successfully restored ovarian function by modifying the Treg/Th17 cell ratio in mice with POI. Nevertheless, the significance and mechanism of HCQ in patients with autoimmune POI must be confirmed in numerous randomized controlled studies and clinical trials.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

Shuai

She

Diao

et al. 2023

American J Rep Immunol

View full text Add to dashboard Cite

Aims:The role of hydroxychloroquine (HCQ) in premature ovarian insufficiency (POI) remains unclear. The purpose of this study was to evaluate the effect of HCQ on ovarian function in mice with POI and to clarify its potential mechanisms.Methods: POI was induced in mice by injection with zona pellucida 3 peptide (pZP3), and HCQ was administered intragastrically. Stages of the estrous cycle were determined using vaginal cytology. The ovarian structure was observed under a microscope after hematoxylin-eosin staining. The levels of serum hormones and anti-ZP antibody (aZPAb) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of CD4, CD45, and ZP2, ZP3 were determined using immunofluorescence and immunohistochemistry, respectively. The T regulatory (Treg)/ T helper 17 (Th17) cell ratio was analyzed using flow cytometry analysis. Western blotting was performed to assess the expression levels of proteins, transcription factors and cytokines.Results: Administration of HCQ to mice with POI greatly restored their estrus cycle. In the treatment group compared to the POI group, estradiol (E 2 ) levels were higher, and follicle stimulating hormone (FSH) levels were lower. In addition, following pZP3, HCQ treatment increased ZP2 and ZP3 expression. Additionally, by inhibiting the activation of the TLR7 signaling pathway, HCQ attenuated the infiltration of inflammatory cells and prevented the activated naive CD4 + T cells from developing into Th17 cells. Conclusion:Our findings showed that HCQ effectively restored ovarian function by altering the Treg/Th17 cell ratio in mice with POI, indicating that HCQ maybe a promising therapeutic method for patients with POI. K E Y W O R D S hydroxychloroquine (HCQ), premature ovarian insufficiency (POI), ovarian function, T regulatory (Treg) cells, T helper 17 (Th17) cells Ling Shuai and Jiajie She contributed equally to this work.

show abstract

Section: Discussionmentioning

confidence: 94%

“…Additionally, APC use MHC class II molecules to deliver antigens to naïve CD4 + T cells 31,32 . Through T cell receptor (TCR), naïve CD4 + T cells can pick up the matching antigens' molecular signals 33,34 . Naïve CD4 + T cells are prone to differentiate into Th17 cells under the influence of pro‐inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

Shuai

She

Diao

et al. 2023

American J Rep Immunol

View full text Add to dashboard Cite

show abstract

“…The transcriptional and signaling pathways underpinning T H 2 lineage polarization are well characterized, with GATA3 and STAT6 playing central roles (32). More recently in the context of allergic asthma, NF-κB signaling has been implicated in GATA3 induction and subsequent T H 2 polarization (30).…”

Section: Resultsmentioning

confidence: 99%

BLOC1S1 control of vacuolar organelle fidelity modulates T_H2 cell immunity and allergy susceptibility

Sharma,

Wu,

Han

et al. 2024

Preprint

View full text Add to dashboard Cite

The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4+ T cells, may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity. Transcript levels of the canonical transcription factors driving CD4+T cell polarization in response to activation showed that, the TH2 regulator GATA3 and phosphorylated STAT6 were preferentially induced in BLOC1S1 depleted primary CD4+ T (TKO) cells. In parallel, in response to both T cell receptor activation and in response to TH2 polarization the levels of IL-4, IL-5 and IL-13 were markedly induced in the absence of BLOC1S1. At the organelle level, mitochondrial DNA leakage evoked cGAS-STING and NF-kB pathway activation with subsequent TH2 polarization. The induction of autophagy with rapamycin reduced cytosolic mtDNA and reverses these TH2 signatures. Furthermore, genetic knockdown of STING and STING and NF-kappaB inhibition ameliorated this immune regulatory cascade in TKO cells. Finally, at a functional level, TKO mice displayed increased susceptible to allergic conditions including atopic dermatitis and allergic asthma. In conclusion, BLOC1S1 depletion mediated disruption of mitochondrial integrity to initiate a predominant TH2 responsive phenotype via STING-NF-kappaB driven signaling of the canonical TH2 regulatory program.

show abstract

“…MALT1 might promote the activation of TCR signaling, which is a vital inducer of both inflammation and oxidative stress ( Mustafa et al, 2021 ). MALT1 could increase the polarization of M1 macrophages and Th17 cells, which release proinflammatory cytokines such as TNF-α, IL-1, and IL-17, thus resulting in a higher level of inflammation ( Wang et al, 2019 ; Meitei and Lal, 2022 ). However, IL-10 showed no difference with MALT1 overexpression or knockdown.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages can be polarized into two different phenotypes, M1 and M2 macrophages, among which M1 macrophages mainly secrete cytokines such as TNF-α and IL-1 to induce inflammation, thus protecting against microbiome infection, whereas M2 macrophages exert protection against parasitic infection and wound healing effects ( Wang et al, 2019 ). Naïve CD4 + T cells can polarize into Th1, Th2, Th17, Treg, etc., and exert immune regulatory effects ( Meitei and Lal, 2022 ). During sepsis, these immune cells are dysregulated, which induces inflammation and potentially causes organ dysfunction ( Martin et al, 2020 ; Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

et al. 2023

View full text Add to dashboard Cite

ObjectiveMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates the inflammatory immune response and organ dysfunction, which are closely implicated in sepsis pathogenesis and progression. This study aimed to explore the role of MALT1 in sepsis-induced organ injury, immune cell dysregulation, and inflammatory storms.MethodsSeptic mice were constructed by intraperitoneal injection of lipopolysaccharide, followed by overexpression or knockdown of MALT1 by tail vein injection of the corresponding lentivirus. Mouse naïve CD4+ T cells and bone marrow-derived macrophages were treated with MALT1 overexpression/knockdown lentivirus plus lipopolysaccharide.ResultsIn the lungs, livers, and kidneys of septic mice, MALT1 overexpression exaggerated their injuries, as shown by hematoxylin and eosin staining (all p < 0.05), elevated cell apoptosis, as reflected by the TUNEL assay and cleaved caspase-3 expression (p < 0.05 in the lungs and kidneys), and promoted macrophage infiltration, as illustrated by CD68 immunofluorescence (p < 0.05 in the lungs and kidneys). Meanwhile, in the blood, MALT1 overexpression reduced T-helper (Th)1/Th2 cells, increased Th17/regulatory T-cell ratios (both p < 0.05), promoted systematic inflammation, as revealed by tumor necrosis factor-α, interleukin-6, interleukin-1β, and C-reactive protein (all p < 0.05), elevated oxidative stress, as shown by nitric oxide (p < 0.05), superoxide dismutase, and malondialdehyde (p < 0.05), and enhanced liver and kidney dysfunction, as revealed by an automatic animal biochemistry analyzer (all p < 0.05 except for aspartate aminotransferase). However, MALT1 knockdown exerted the opposite effect as MALT1 overexpression. Ex vivo experiments revealed that MALT1 overexpression promoted the polarization of M1 macrophages and naïve CD4+ T cells toward Th2 and Th17 cells (all p < 0.05), while MALT1 knockdown attenuated these effects (all p < 0.05). Mechanistically, MALT1 positively regulated the nuclear factor-κB (NF-κB) pathway both in vivo and ex vivo (p < 0.05).ConclusionMucosa-associated lymphoid tissue lymphoma translocation protein 1 amplifies multiple organ injury, inflammation, oxidative stress, and imbalance of macrophages and CD4+ T cells by activating the NF-κB pathway in sepsis.

show abstract

T cell receptor signaling in the differentiation and plasticity of CD4+ T cells

Cited by 16 publications

References 235 publications

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

BLOC1S1 control of vacuolar organelle fidelity modulates T_H2 cell immunity and allergy susceptibility

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

Contact Info

Product

Resources

About

T cell receptor signaling in the differentiation and plasticity of CD4+ T cells

Cited by 16 publications

References 235 publications

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice

BLOC1S1 control of vacuolar organelle fidelity modulates TH2 cell immunity and allergy susceptibility

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

Contact Info

Product

Resources

About

BLOC1S1 control of vacuolar organelle fidelity modulates T_H2 cell immunity and allergy susceptibility