CD40-CD154: A perspective from type 2 immunity

Díaz, Álvaro; González-Alayón, Ignacio; Pérez-Torrado, Valentina; Suárez-Martins, Mariana

doi:10.1016/j.smim.2021.101528

Cited by 13 publications

(7 citation statements)

References 132 publications

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“…CD40-CD40L is required for induction of Th1 and Th17 responses and driving release of corresponding inflammatory factors to eliminate pathogens (14). Absence of the CD40-CD40L interaction leads to impairment of CD4 + T-cell priming by dendritic cells, CD4 + T-cell helping of B cells and classic macrophage activation by CD4 + T cells (15,16). ITK (IL2-inducible T-cell kinase), a component of T-cell receptor signaling pathways, also participates in molecular pathway driving T helper cell differentiation and cytokine production (17,18).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics applications under condition control: high diagnostic value of DDX47 in real medical settings

Zhu

Cai

Zheng

et al. 2023

Shock

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Sepsis is an organ dysfunction caused by a dysregulated host response to infection and remains an ongoing threat to human health worldwide. Septic shock is the most severe subset of sepsis as characterized by abnormalities in cells, circulation and metabolism. As a time-dependent condition, early recognition allowing appropriate therapeutic measures to be started in a timely manner become the most effective way to improve prognosis. However, due to the lack of a gold standard, most diagnoses merely rely on medical history, empirical diagnosis and blood culture results. Gene expression profiles have specific diagnostic value, as they reflect a subjective host response to pathogens. We propose a method, Condition Control based on Real-life Medical Scenarios, to control for factors in realistic medical scenarios. Restricted variables are used as much as possible to identify unique differential genes and progressively test their diagnostic value by relaxing restrictions. In total, three datasets were included in the study; the first two datasets were from the Gene Expression Omnibus (GEO) database, and the third involved patients who were diagnosed with sepsis or septic shock within 7 days of admission to the ICU at West China Hospital of Sichuan University from 2020 to 2021. DDX47 showed preferable diagnostic value in various scenarios, especially in patients with common infections or sepsis and septic shock. Here we also show that hub genes may regulate immune function and immune cell counts through the interaction of different apoptotic pathways and immune checkpoints based on the high correlation. DDX47 is closely associated with B cells according to single-cell sequencing results.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics applications under condition control: high diagnostic value of DDX47 in real medical settings

Zhu

Cai

Zheng

et al. 2023

Shock

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“…CD154 can promote CD40 aggregation after intercalation with CD40 and mediate the relevant signals through TNFR‐associated factors (TRAFs) (Zarzycka et al, 2015). CD40/CD154, as costimulatory molecules, play a key regulatory role in the immune response (Díaz et al, 2021). The immune system plays roles in supervising, regulating, and responding to external factors in a stressful manner, and also in causing optic nerve damage (Southey et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Research studies have revealed the presence of significant autoimmune reactions in patients with different types of GC (Geyer & Levo, 2020; Southey et al, 2021; Wang & Wei, 2021). Therefore, further exploration of key immune‐related molecules might provide potential targets for immunomodulatory therapy of OHG.CD40/CD154 (CD40L), as a costimulatory signal for T cell activation, plays a key role in several aspects of the immune response (Díaz et al, 2021). CD40 is mainly expressed on the surface of antigen‐presenting cells (APCs), (Vonderheide, 2020) To our knowledge, CD154 plays an important regulatory role in Müller cells (Portillo et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential

Liu

Nie

et al. 2023

Cell Biology International

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An elevation of pathologic intraocular pressure (IOP) is the greatest risk factor for glaucoma. CD154 has been reported to bind to CD40 expressed by orbital fibroblasts and be involved in immune and inflammatory responses. However, the function and mechanism of CD154 in ocular hypertensive glaucoma (OHG) are not fully understood. We isolated and characterized Müller cells and subsequently examined the effect of CD154 on ATP release from those cells. After being cocultured with CD154-pretreated Müller cells, retinal ganglion cells (RGCs) were treated with P2X7 siRNAs or a P2X7 inhibitor. Furthermore, mouse models of glaucoma (GC) were injected with P2X7 shRNA. p21, p53, and P2X7 expression were examined, and cellular senescence and apoptosis were detected by β-Gal and TUNEL staining, retinal pathology was examined by H&E staining, and CD154 and β-Gal expression were detected by ELISA. CD154 induced ATP release from Müller cells and accelerated the senescence and apoptosis of RGCs that had been cocultured with Müller cells. We also found that treatment with P2X7 could attenuate the senescence and apoptosis of RGCs mediated by Müller cells pretreated with CD154. In vivo studies in GC model mice verified that P2X7 silencing attenuated pathological damage and prevented the senescence and apoptosis of retinal tissue. The study demonstrates how CD154 accelerates the aging and apoptosis of RGCs by co-cultivating Müller cells pretreated with CD154 in OHG. The research implies that CD154 has the potential to become a new therapeutic target for ocular hypertension glaucoma, providing a new research direction for its treatment.

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“…The assay was read using the Bio-Plex Multiplex Immunoassay System (Bio-Rad). To analyse the cytokine pattern in response to MABSC lysate, we combined the concentration values of different cytokines by adding them together and called them T helper (Th)1 (IFN-γ + TNF-α + IL-2), Th2 (CD40L + IL-4 + IL-5) and Th17 (IL-17) cytokine levels ( Mousset et al., 2019 ; Díaz et al., 2021 ). The cytokine concentrations were firstly expressed in picograms per mL (pg/mL).…”

Section: Methodsmentioning

confidence: 99%

Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity

Mauch

Jensen

Qvist

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundWe aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels.MethodsIn this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood.ResultsAll CF/MABSC patients had increased CD3+ and CD19+ lymphoblast formation upon PBMC stimulation with MABSC lysate. There was a higher rate of CD3+ than CD19+ lymphoblasts, predominance of CD4+ over CD8+ lymphoblasts, IFN-γ, TNF-α and IL-2 production, low production of the Th17-associated IL-17, and discrete or no production of Th2/B cell-associated cytokines soluble CD40 ligand (CD40L), IL-4 and IL-5, indicating a Th1-dominated phenotype and infection restricted to the lungs. A similar pattern was seen in C/BCG+ controls, and CF/MAC patients, pointing to cross-reactivity. MABSC-IgG levels were higher in CF/MABSC patients than in both control groups, but not CF/NTM- patients, most of whom also had CD3+ and/or CD19+ lymphoblast formation upon PBMC stimulation, indicating previous exposure, subclinical or latent infection with MABSC or other NTM.ConclusionThe anti-MABSC immune response is Th1-skewed and underlines the cross-reactivity in the anti-mycobacterial immune response. The results, together with published clinical observations, indicate that BCG vaccination may cross-react against NTM in CF patients, and this should be investigated. Due to cross-reactivity, it would also be interesting to investigate whether a combination of MABSC-induced cytokine production by blood cells and anti-MABSC IgG measurement can be useful for identifying latent or subclinical infection both with MABSC and other NTM in CF patients.

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CD40-CD154: A perspective from type 2 immunity

Cited by 13 publications

References 132 publications

Bioinformatics applications under condition control: high diagnostic value of DDX47 in real medical settings

Bioinformatics applications under condition control: high diagnostic value of DDX47 in real medical settings

Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential

Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity

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