The Impaired Balance of CD4+/CD8+ Ratio in Patients with Chronic Hepatitis B

Shokoohifar, Nesa; Ahmady‐Asbchin, Salman; Besharat, Sima; Roudbari, Fatemeh; Mohammadi, Saeed; Amiriani, Taghi; Khodabakhshi, Behnaz; Norouzi, Alireza; Shahabinasab, Iman

doi:10.5812/hepatmon.96799

Cited by 5 publications

(1 citation statement)

References 14 publications

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“…The secretion of HBV-mediated pro-and anti-inflammatory cytokines from effector immune cells, such as IFNγ, IFNα, IL1, IL10, IL6, etc., are deregulated during CHB [5][6][7]. The impairment of innate immunity [8], in addition to the consequent flawed maturation of adaptive immune cells [9], leaves the CHB patients vulnerable to the uncontrolled replication of HBV [10].…”

Section: Introductionmentioning

confidence: 99%

Rosuvastatin Intervention in Patients with Chronic Hepatitis B (CHB) Expands CD14+ CD16− Classical Monocytes via Aryl Hydrocarbon Receptor (AHR)

Rahmati,

Zare Ebrahimabad,

Langari

et al. 2024

Immuno

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Chronic hepatitis B (CHB) poses treatment challenges, with treatment response and disease outcome often determined by the immune response, particularly mononuclear phagocytes. Monocytes can differentiate into various subpopulations influenced by AHR. Statins, known for inflammation modulation, may impact monocyte function via AHR activation. This study explored rosuvastatin (RSV)’s effects on monocyte subtypes, inflammatory markers, and AHR in CHB patients. Fifteen CHB patients were randomly assigned to receive either 20 mg RSV or a placebo daily for three months. Flow cytometry assessed CD14+ CD16− (classical), CD14+ CD16+ (intermediate), and CD14dim CD16+ (patrolling) monocyte subtypes, along with AHR levels in each subset. ELISA quantified cytokines IL-6, IFN-γ, IL-12, IL-10, TNF-α, TGF-β, and IL-1β. RSV expanded CD14+ CD16− classical and reduced CD14+ CD16+ intermediate monocytes in CHB patients while increasing AHR+ cell percentages in all subsets. RSV treatment upregulated key AHR target genes (Cyp1a1, Cyp1b1, and ARNT), indicating robust AHR signaling activation. It also reduced pro-inflammatory cytokine levels (IL-6, IFNγ, IL-12, TNF-α) and elevated anti-inflammatory cytokines (IL-10, TGF-β). Thus, RSV may modulate the immune response by altering monocyte subtypes in CHB patients via AHR activation.

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Section: Introductionmentioning

confidence: 99%

Rosuvastatin Intervention in Patients with Chronic Hepatitis B (CHB) Expands CD14+ CD16− Classical Monocytes via Aryl Hydrocarbon Receptor (AHR)

Rahmati,

Zare Ebrahimabad,

Langari

et al. 2024

Immuno

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Microplastics exposure induced and exacerbated the development of systemic lupus erythematosus in mice

Chen,

Wan,

Qiu

et al. 2024

Science of The Total Environment

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Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells

Thongchot,

Aksonnam,

Prasopsiri

et al. 2024

BMC Med

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Background Triple-negative breast cancer (TNBC), known for its aggressiveness and limited treatment options, presents a significant challenge. Adoptive cell transfer, involving the ex vivo generation of antigen-specific T cells from peripheral blood mononuclear cells (PBMCs), emerges as a promising approach. The overexpression of mesothelin (MSLN) and nucleolin (NCL) in TNBC samples underscores their potential as targets for T cell therapy. This study explored the efficacy of multi-peptide pulsing of PBMCs to generate MSLN/NCL-specific T cells targeting MSLN+/NCL+ TNBC cells. Methods TNBC patient samples were confirmed for both MSLN and NCL expression via immunohistochemistry. Synthesized MSLN and NCL peptides were combined and administered to activate PBMCs from healthy donors. The cancer-killing ability of the resultant T cells was assessed using crystal violet staining, and their subtypes and cytotoxic cytokines were characterized through flow cytometry and cytokine bead array. Results Findings showed that 85.3% (127/149) of TNBC cases were positive for either MSLN or NCL, or both; with single positivity rates for MSLN and NCL of 14.1% and 28.9%, respectively. MSLN and NCL peptides, with high binding affinity for HLA-A*02, were combined and introduced to activated PBMCs from healthy donors. The co-pulsed PBMCs significantly induced TEM and TEMRA CD3+/CD8+ T cells and IFN-γ production, compared to single-peptide pulsed or unpulsed conditions. Notably, MSLN/NCL-specific T cells successfully induced cell death in MSLN+/NCL+ MDA-MB-231 cells, releasing key cytotoxic factors such as perforin, granzymes A and B, Fas ligand, IFN-γ, and granulysin. Conclusions These findings serve as a proof-of-concept for using multiple immunogenic peptides as a novel therapeutic approach in TNBC patients.

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The Impaired Balance of CD4+/CD8+ Ratio in Patients with Chronic Hepatitis B

Cited by 5 publications

References 14 publications

Rosuvastatin Intervention in Patients with Chronic Hepatitis B (CHB) Expands CD14+ CD16− Classical Monocytes via Aryl Hydrocarbon Receptor (AHR)

Rosuvastatin Intervention in Patients with Chronic Hepatitis B (CHB) Expands CD14+ CD16− Classical Monocytes via Aryl Hydrocarbon Receptor (AHR)

Microplastics exposure induced and exacerbated the development of systemic lupus erythematosus in mice

Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells

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