Phenotypic features of innate lymphoid cells in rheumatoid arthritis

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Abstract

Currently, rheumatoid arthritis (RA) is considered among the most common autoimmune diseases worldwide, being associated with progressing disability, systemic organ and tissue lesions, as well as social and economic losses for the state. Studies of innate lymphoid cells (ILS) seems to be actual and significant when studying development of autoimmune inflammation in RA, in particular, the issues of the cell plasticity. ILC represent tissue resident lymphoid cells that display functional diversity, like as T cells. Moreover, ILC regulate orientation of immune response by means of cytokine production. Small amounts of ILCs are present in the bloodstream, presumably for migration to target organs and tissues. Accordingly, the study of ILC in RA will promote understanding of the RA pathogenesis. It is also possible in the future to develop new therapeutic strategies based on the impact on the immunological balance, as well as reducing the inflammatory process in RA. The aim of this study was to determine the subpopulation composition and phenotypic features of ILCs in RA.

We have isolated and studied peripheral blood mononuclear cells (PBMC) from 7 patients with RA and 6 healthy donors. The isolated blood MNCs were stained with monoclonal antibodies conjugated to fluorochromes: lineage-specific (CD3/14/16/19/20/56) and anti-FceR1 alpha-FITC, anti-CD294-APC/Cy7, anti-CD127-PerCP/Cy5.5, anti-CD336-PE, anti-CD117-APC. ILCs were defined as Lin-CD127+. The numbers of CD294+ILCs (ILC2) were estimated in the general population, CD117-CD294-ILCs were defined as ILC1, and CD117+CD294-ILCs, as ILC3. The cell phenotype was analyzed with a FACS Canto II flow cytometer (BD Biosciences, USA).

We determined relative numbers of different ILC subpopulations (ILC1, ILC2, and ILC3) among the total blood MNCs. It was shown, that the number of ILC2 cells in RA patients was statistically significantly reduced compared to healthy donors, whereas no significant differences in percentage of ILC1 and ILC3 were revealed between donors and patients. We also evaluated the amount of c-Kit+ILC2; there were no significant differences in the proportion of these cells between donors and patients.

ILCs represent a population of cells that contribute to the RA pathogenesis. The role of ILC2 in RA is, presumably, protective. The ILC imbalance may contribute to the development of RA. For a better understanding of the RA pathogenesis, further studies of the subpopulation profile, phenotypic and functional characteristics of ILC are required in this disorder.

About the authors

O. S. Boeva

Research Institute of Fundamental and Clinical Immunology; Novosibirsk National Research State University

Author for correspondence.
Email: starchenkova97@gmail.com

Researcher Laboratory Assistant, Laboratory of Clinical Immunopathology; Student

Russian Federation, Novosibirsk; Novosibirsk

M. T. Berishvili

Research Institute of Fundamental and Clinical Immunology; Novosibirsk State Medical University

Email: starchenkova97@gmail.com

Researcher Laboratory Assistant, Laboratory of Clinical Immunopathology; Student

Russian Federation, Novosibirsk; Novosibirsk

A. E. Sizikov

Research Institute of Fundamental and Clinical Immunology

Email: starchenkova97@gmail.com

PhD (Medicine), Head, Department of Rheumatology, Acting Chief Physician of the Immunopathology Clinic

Russian Federation, Novosibirsk

E. A. Pashkina

Research Institute of Fundamental and Clinical Immunology

Email: starchenkova97@gmail.com

PhD (Biology), Senior Research Associate, Laboratory of Clinical Immunopathology

Russian Federation, Novosibirsk

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Supplementary files

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2. Figure 1. Number of different ILC subpopulations in normal and rheumatoid arthritis

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3. Figure 2. Number of c-Kit+ILC2 in normal and rheumatoid arthritis patients

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Copyright (c) 2022 Boeva O.S., Berishvili M.T., Sizikov A.E., Pashkina E.A.

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