Content of myeloid-derived suppressor cells in autoimmune diseases in children

Abstract

Myeloid-derived suppressor cells (MDSCs) play an important role in regulation of immune response. An increase in their number in adult patients with autoimmune diseases has been reported. G-MDSCs, M-MDSCs, and MDSCs(M-G-) at different stages of autoimmune disease may both activate T cell proliferation, leading to disease progression, or inhibit it, thus promoting Treg differentiation. Arginase-1 (Arg- 1) is an enzyme in MDSCs that reduces the concentration of arginine required for T lymphocyte proliferation. Our aim was to evaluate the content of MDSCs populations and functional activity of MDSCs in children with autoimmune diseases. 75 children with inflammatory bowel diseases (IBD), 60 children with multiple sclerosis (MS), 69 children with psoriasis (PS), 62 healthy age-matched children were included into the study. The content of MDSCs ((CD3, CD19, CD56, HLA-DR)-, CD11b+ and CD33+), subpopulations of MDSCs (M-MDSCs, G-MDSCs expressing CD14 and CD15), assessment of Arg-1 activity were performed by flow cytometry techniques. The content of MDSCs in patients with IBD, MS and PS was significantly higher than in the comparison group and depended on the state of exacerbation/remission. In exacerbation and remission of IBD, MS and PS, a significant increase of MDSCs was revealed when compared with healthy children; the highest values were found in children in exacerbation of MS (Me-3.5 (2.5-5.6) % MNC against Me-1.6 (0.9-2.5) % MNC, p 0.001). In patients with MS, the content of G-MDSC, M-MDSC was significantly higher, and MDSC(M-G-) was lower than in healthy children. An increase in absolute amounts of G-MDSCs was shown in MS exacerbation compared to the disease remission state (p = 0.022). For patients with IBD, a significant increase in percentage of MDSCs and M-MDSCs (p = 0.014 and p = 0.045, respectively) was obtained in exacerbation of the disease relative to remission state. In patients with IBD, MS, and PS, a significant increase in Arg-1 activity in MDSCs was found, with a decreased number of MDSCs in patients in remission compared to exacerbation phase of the disease. In children with autoimmune diseases, an increase in the MDSC populations was found. The activity of arginase-1 in MDSCs is increased in remission, along with a decrease in their numbers.