Objective: This work aims to investigate whether RIP2 silencing in naive CD4 T cells from lupus-prone mice impacts Th17 cell activity or differentiation in vitro.
Methods: Naive CD4 T cells isolation from MRL/lpr mice's spleens. Three RNA interference target sequences of RIP2 were packaged with lentivirus and transfected into naive CD4 T cells. The shRIP2 with the highest interference efficiency was selected and transfected into naive CD4 T cells. Naive CD4 T cells were cultured under conventional (TGF-β1 and IL-6) and pathogenic (IL-6, IL-23, IL-1β) differentiation environments, respectively. Then, RT-qPCR, Western blot or Flow Cytometry were used for measuring the amounts of RIP2 and IL-17 and the differentiation of Th17 cells in two settings.
Results: Under the conventional Th17 (cTh17) cell differentiation environment (TGF-β1 and IL-6), RIP2 deficiency is linked to decreased IL-17A levels (1.00 ± 0.03 vs 0.80 ± 0.03) and attenuated cTh17 cell (2.46 ± 0.08 vs 0.78 ± 0.03) differentiation (all, P < 0.05). Under the pathogenic Th17 (pTh17) cell environment (IL-1β, IL-23, IL-6), RIP2 deficiency is linked to elevated IL-17A levels (1.03 ± 0.05 vs 1.63 ± 0.07) and enhanced pTh17 cell (3.69 ± 0.19 vs 5.49 ± 0.10) differentiation (all, P < 0.05).
Conclusion: Our data suggest that RIP2 inhibition induces preferential differentiation of naive CD4 T cells to pathogenic Th17 cells, while being able to upregulate IL-17A levels in the context of pTh17 cell differentiation. Our study opens up new research areas to reveal the underlying mechanisms and potential therapeutic targets for the prevention and treatment of SLE patients. Key Points • Silencing of RIP2 in naive CD4 T cells from lupus-prone mice promotes pathogenic Th17 (pTh17) cell differentiation and IL-17A production under pTh17 cell (IL-1β, IL-23, and IL-6) conditions. • RIP2 deficiency in naive CD4 T cells reduces conventional Th17 (cTh17) cell differentiation and IL-17A production under cTh17 cell (TGF-β1 and IL-6) conditions. • RIP2-deficient naive CD4 T cells preferentially differentiate towards pTh17 cells rather than cTh17 cells in vitro. • Inhibition of RIP2 may be involved in the development of SLE via effects on Th17/IL-17.
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http://dx.doi.org/10.1007/s10067-024-07124-x | DOI Listing |
Alzheimers Dement
December 2024
All India Institute of Medical Sciences, Nagpur, Nagpur, Maharashtra, India.
Background: Multiple Sclerosis (MS) is a chronic, etiologically complex disease of the central nervous system (CNS) characterized by inflammation, demyelination, and neuronal damage. MS has seven categories based on disease course. Seventy to eighty percent of individuals with MS initially develop a clinical pattern with periodic relapses and remissions, called relapsing-remitting MS (RRMS).
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Massachusetts Chan Medical School, Worcester, MA, USA.
Background: Alzheimer's disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. However, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
December 2024
Department of Infection and Immunology, Changsha First Hospital, Changsha 410005, China.
Objective To clarify the mechanism that HIV infection mediates mitochondrial damage of CD4 T lymphocytes (CD4 T cells) through mitogen-activated protein kinase (MAPK) pathway. Methods From October 1st, 2022 to March 31st, 2023, 47 HIV-infected people who received antiretroviral therapy (ART) for 4 years were recruited, including 22 immune non-responders (INR) and 25 responders (IR); and 26 sex and age-matched control participants (HC) who were negative for HCV, HBV, and HIV infections. The immune parameters were analyzed by flow cytometry.
View Article and Find Full Text PDFMucosal Immunol
December 2024
Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Haihe Laboratory of Cell Ecosystem, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address:
Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E (PGE), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner.
View Article and Find Full Text PDFAging Cell
January 2025
National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.
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