The immunoregulatory function of peripheral blood CD71⁺ erythroid cells in systemic-onset juvenile idiopathic...

Area of Science:

• Immunology
• Hematology
• Pediatric Rheumatology

Background:

• CD71-positive erythroid cells (CECs) possess immunoregulatory functions through cell-cell interactions and mediators.
• CECs are observed in newborns and individuals with hemolytic or cardiopulmonary conditions.
• The role of CECs in systemic inflammation, particularly in SoJIA, requires further investigation.

Purpose of the Study:

• To investigate the biological role and function of CECs in systemic-onset juvenile idiopathic arthritis (SoJIA).
• To analyze gene expression and functional characteristics of CECs in active SoJIA patients.

Main Methods:

• Analysis of gene expression in peripheral blood mononuclear cells from SoJIA patients.
• Quantification of circulating CECs and correlation with inflammatory markers (CRP, IL-6, IL-18, sTNF-R).
• Co-culture experiments involving SoJIA-derived CECs and healthy donor monocytes, including arginase inhibition.

Main Results:

• SoJIA patients exhibited upregulated erythropoiesis-related genes and the largest expansion of CECs among inflammatory diseases.
• Serum erythropoietin and hepcidin levels correlated with CEC counts in SoJIA.
• CEC counts positively correlated with inflammatory markers like CRP, IL-6, IL-18, and soluble TNF receptors.
• Co-culture with SoJIA CECs suppressed IL-1β, IL-6, and IL-8 secretion from monocytes, even with an arginase inhibitor.
• ARG2 was the top upregulated gene in SoJIA CECs compared to controls.

Conclusions:

• CECs significantly increase in the periphery during the acute phase of SoJIA, exceeding levels in other inflammatory diseases.
• Circulating CECs may mitigate excessive inflammation in SoJIA through immunoregulatory pathways, potentially involving arginase-2.