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

• Main Authors: Soumya Sengupta (Author), Gargee Bhattacharya (Author), Subhasmita Mohanty (Author), Shubham K. Shaw (Author), Gajendra M. Jogdand (Author), Rohila Jha (Author), Prakash K. Barik (Author), Jyoti R. Parida (Author), Satish Devadas (Author)
• Format: Book
• Published: MDPI AG, 2023-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

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.

Item Description

10.3390/antiox12010181
2076-3921