Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Sengupta, Soumya, Bhattacharya, Gargee, Mohanty, Subhasmita, Shaw, Shubham K., Jogdand, Gajendra M., Jha, Rohila, Barik, Prakash K., Parida, Jyoti R., Devadas, Satish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855022/
https://www.ncbi.nlm.nih.gov/pubmed/36671045
http://dx.doi.org/10.3390/antiox12010181
_version_ 1784873275536441344
author Sengupta, Soumya
Bhattacharya, Gargee
Mohanty, Subhasmita
Shaw, Shubham K.
Jogdand, Gajendra M.
Jha, Rohila
Barik, Prakash K.
Parida, Jyoti R.
Devadas, Satish
author_facet Sengupta, Soumya
Bhattacharya, Gargee
Mohanty, Subhasmita
Shaw, Shubham K.
Jogdand, Gajendra M.
Jha, Rohila
Barik, Prakash K.
Parida, Jyoti R.
Devadas, Satish
author_sort Sengupta, Soumya
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9855022
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98550222023-01-21 IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology Sengupta, Soumya Bhattacharya, Gargee Mohanty, Subhasmita Shaw, Shubham K. Jogdand, Gajendra M. Jha, Rohila Barik, Prakash K. Parida, Jyoti R. Devadas, Satish Antioxidants (Basel) Article 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. MDPI 2023-01-12 /pmc/articles/PMC9855022/ /pubmed/36671045 http://dx.doi.org/10.3390/antiox12010181 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sengupta, Soumya
Bhattacharya, Gargee
Mohanty, Subhasmita
Shaw, Shubham K.
Jogdand, Gajendra M.
Jha, Rohila
Barik, Prakash K.
Parida, Jyoti R.
Devadas, Satish
IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title_full IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title_fullStr IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title_full_unstemmed IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title_short IL-21, Inflammatory Cytokines and Hyperpolarized CD8(+) T Cells Are Central Players in Lupus Immune Pathology
title_sort il-21, inflammatory cytokines and hyperpolarized cd8(+) t cells are central players in lupus immune pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855022/
https://www.ncbi.nlm.nih.gov/pubmed/36671045
http://dx.doi.org/10.3390/antiox12010181
work_keys_str_mv AT senguptasoumya il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT bhattacharyagargee il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT mohantysubhasmita il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT shawshubhamk il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT jogdandgajendram il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT jharohila il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT barikprakashk il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT paridajyotir il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology
AT devadassatish il21inflammatorycytokinesandhyperpolarizedcd8tcellsarecentralplayersinlupusimmunepathology