IL-21, Inflammatory Cytokines and Hyperpolarized CD8 + T Cells Are Central Players in Lupus Immune Pathology

Systemic lupus erythematous (SLE) is a chronic autoimmune disorder, broadly characterized by systemic inflammation along with heterogeneous clinical manifestations, severe morbidity, moribund organ failure and eventual mortality. In our study, SLE patients displayed a higher percentage of activated,...

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Bibliographic Details
Published in:Antioxidants 2023-01, Vol.12 (1), p.181
Main Authors: Sengupta, Soumya, Bhattacharya, Gargee, Mohanty, Subhasmita, Shaw, Shubham K, Jogdand, Gajendra M, Jha, Rohila, Barik, Prakash K, Parida, Jyoti R, Devadas, Satish
Format: Article
Language:English
Subjects:
antioxidant
Antioxidants
Autoimmune diseases
CD8 antigen
CD8+ T cells
Cell differentiation
Cytokines
Cytotoxicity
Disease
Genotype & phenotype
Homeostasis
IL-21
Infections
Inflammation
inflammatory cytokines
Interleukin 21
Lupus
Lymphocytes
Lymphocytes T
Morbidity
Oxidants
Oxidative stress
Pathogens
Pathology
Phenotypes
Polarization
reactive oxygen species
SLE
Systemic lupus erythematosus
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Summary:Systemic lupus erythematous (SLE) is a chronic autoimmune disorder, broadly characterized by systemic inflammation along with heterogeneous clinical manifestations, severe morbidity, moribund organ failure and eventual mortality. In our study, SLE patients displayed a higher percentage of activated, inflamed and hyper-polarized CD8 T cells, dysregulated CD8 T cell differentiation, significantly elevated serum inflammatory cytokines and higher accumulation of cellular ROS when compared to healthy controls. Importantly, these hyper-inflammatory/hyper-polarized CD8 T cells responded better to an antioxidant than to an oxidant. Terminally differentiated Tc1 cells also showed plasticity upon oxidant/antioxidant treatment, but that was in contrast to the SLE CD8 T cell response. Our studies suggest that the differential phenotype and redox response of SLE CD8 T cells and Tc1 cells could be attributed to their cytokine environs during their respective differentiation and eventual activation environs. The polarization of Tc1 cells with IL-21 drove hyper-cytotoxicity without hyper-polarisation suggesting that the SLE inflammatory cytokine environment could drive the extreme aberrancy in SLE CD8 T cells.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox12010181