Insufficient PD-1 expression during active autoimmune responses: a deep single-cell proteomics analysis in inflammatory arthritis.

Autor:	Vetsika EK; Centre of New Biotechnologies and Precision Medicine (CNBPM), School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Fragoulis GE; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Kyriakidi M; Centre of New Biotechnologies and Precision Medicine (CNBPM), School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Verrou KM; Centre of New Biotechnologies and Precision Medicine (CNBPM), School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Tektonidou MG; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Alissafi T; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Laboratory of Immune Regulation, Center of Basic Sciences, Biomedical Research Foundation Academy of Athens, Athens, Greece., Sfikakis PP; Centre of New Biotechnologies and Precision Medicine (CNBPM), School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jun 07; Vol. 15, pp. 1403680. Date of Electronic Publication: 2024 Jun 07 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1403680
Abstrakt:	Objectives: Programmed cell death protein-1 (PD-1) maintains peripheral immune tolerance by preventing T cell continuous activation. Aiming to understand the extent of PD-1 expression in inflammatory arthritis beyond its involvement with T cells, we assess its presence on various circulating single cells. Methods: Mass cytometry analysis of patients with active seropositive/seronegative rheumatoid (RA; n=9/8) and psoriatic (PsA; n=9) arthritis versus healthy controls (HC; n=13), re-evaluating patients after 3 months of anti-rheumatic treatment. Results: PD-1 was expressed in all leukocyte subpopulations, with the highest PD-1 + cell frequencies in eosinophils (59-73%) and T cells (50-60%), and the lowest in natural-killer cells (1-3%). PD-1 + cell frequencies and PD-1 median expression were comparable between patient subgroups and HC, in the majority of cell subsets. Exceptions included increases in certain T cell/B cell subsets of seropositive RA and specific monocyte subsets and dendritic cells of PsA; an expanded PD-1 + CD4 + CD45RA + CD27 + CD28 + T subset, denoting exhausted T cells, was common across patient subgroups. Strikingly, significant inverse correlations between individual biomarkers of systemic inflammation (ESR and/or serum CRP) and PD-1 + cell frequencies and/or median expression were evident in several innate and adaptive immunity cell subsets of RA and PsA patients. Furthermore, all inverse correlations noted in individuals with active arthritis were no longer discernible in those who attained remission/low disease activity post-treatment. Conclusion: PD-1 expression may be insufficient, relative to the magnitude of the concomitant systemic inflammatory response on distinct leukocyte subsets, varying between RA and PsA. Our results point to the potential therapeutic benefits of pharmacological PD-1 activation, to rebalance the autoimmune response and reduce inflammation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Vetsika, Fragoulis, Kyriakidi, Verrou, Tektonidou, Alissafi and Sfikakis.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu