CD8+ T-Cells in Juvenile-Onset SLE: From Pathogenesis to Comorbidities

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CD8+ T-Cells in Juvenile-Onset SLE: From Pathogenesis to Comorbidities

Ciurtin, Coziana; Pineda-Torra, Ines; Jury, Elizabeth C; Robinson, George A; (2022) CD8+ T-Cells in Juvenile-Onset SLE: From Pathogenesis to Comorbidities. Frontiers in Medicine , 9 , Article 904435. 10.3389/fmed.2022.904435. Green open access

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Abstract

Diagnosis of systemic lupus erythematosus (SLE) in childhood [juvenile-onset (J) SLE], results in a more severe disease phenotype including major organ involvement, increased organ damage, cardiovascular disease risk and mortality compared to adult-onset SLE. Investigating early disease course in these younger JSLE patients could allow for timely intervention to improve long-term prognosis. However, precise mechanisms of pathogenesis are yet to be elucidated. Recently, CD8+ T-cells have emerged as a key pathogenic immune subset in JSLE, which are increased in patients compared to healthy individuals and associated with more active disease and organ involvement over time. CD8+ T-cell subsets have also been used to predict disease prognosis in adult-onset SLE, supporting the importance of studying this cell population in SLE across age. Recently, single-cell approaches have allowed for more detailed analysis of immune subsets in JSLE, where type-I IFN-signatures have been identified in CD8+ T-cells expressing high levels of granzyme K. In addition, JSLE patients with an increased cardiometabolic risk have increased CD8+ T-cells with elevated type-I IFN-signaling, activation and apoptotic pathways associated with atherosclerosis. Here we review the current evidence surrounding CD8+ T-cell dysregulation in JSLE and therapeutic strategies that could be used to reduce CD8+ T-cell inflammation to improve disease prognosis.

Type:	Article
Title:	CD8+ T-Cells in Juvenile-Onset SLE: From Pathogenesis to Comorbidities
Open access status:	An open access version is available from UCL Discovery
DOI:	10.3389/fmed.2022.904435
Publisher version:	https://doi.org/10.3389/fmed.2022.904435
Language:	English
Additional information:	© 2022 Ciurtin, Pineda-Torra, Jury and Robinson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Keywords:	CD8+ T-cells, juvenile-onset SLE, immunopathology, comorbidities, atherosclerosis
UCL classification:	UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI:	https://discovery.ucl.ac.uk/id/eprint/10151294