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Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions.
Front Immunol
December 2024
Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, Japan.
Sepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice, of innate and adaptive immune cells, leading to profound immunological suppression. This severe immune dysfunction hampers effective primary pathogen clearance, thereby increasing the risk of secondary opportunistic infections, latent viral reactivation, multiple organ dysfunction, and elevated mortality.
View Article and Find Full Text PDFCAR-based cell therapies for systemic lupus erythematosus.
Chin Med J (Engl)
December 2024
Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.
The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic AD, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics.
View Article and Find Full Text PDFTOX Does Not Drive Sepsis-Induced T-Cell Exhaustion.
Eur J Immunol
December 2024
The Affiliated Zhongda Hospital, Clinical Medical College, Southeast University, Nanjing, China.
The immune system undergoes profound dysregulation in sepsis, characterized by hyperinflammation in the acute phase followed by long-lasting immunosuppression. T-cell exhaustion has been proposed as one facet of sepsis-related immunosuppression, which is characterized by impaired effector function and continuous expression of PD1. However, the current analysis of T-cell exhaustion in the post-sepsis is inadequate.
View Article and Find Full Text PDFDynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma.
Blood Cancer Discov
December 2024
Sheba Medical Center, New York, NY, United States.
Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immune suppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. Here, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.
View Article and Find Full Text PDFMetformin ameliorates diabetes-induced hepatic ultrastructural damage and the immune biomarker CD86 and inflammation in rats.
Ultrastruct Pathol
December 2024
Department of Family and Community Medicine, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Diabetes is a known inducer of hepatic ultrastructural alterations, and the expression of the immune biomarker that involves in T-cell immunity, cluster of differentiation 86 (CD86) is increased in diabetic patients with liver cirrhosis. The antidiabetic drug metformin has not previously been used to protect against type 2 diabetes mellitus (T2DM)-induced alternations in hepatic ultrastructure and the induction of the hepatic CD86/inflammation axis in diabetic animal models induced by streptozotocin and a high fat diet. To test our hypotheses, T2DM was induced in rats (model group) and the protective animals were treated with the antidiabetic drug metformin (200 mg/kg) until being sacrificed at week 12.
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