The Expansion of CD25 high IL-10 high FoxP3 high B Regulatory Cells Is in Association with SLE Disease Activity.
B regulatory cells (Bregs) belong to a subgroup of activated B cells tasked with maintaining self-tolerance and preventing autoimmunity. While sharing similar regulatory mechanisms such as IL-10 dependency, they also defer in exhibiting their suppressive effects by expressing Fas-Ligand, TGF-beta, and PDL-1. In this study we show, for the first time, the expansion of CD25(high)FoxP3(high) Bregs in systemic lupus erythematosus (SLE) patients compared to healthy individuals (18.5 ± 3.052% versus 11.0 ± 1.654%, p < 0.001, resp.). This expansion was also shown to correlate with SLE disease activity (r = 0.75). In addition, CD25(high)FoxP3(high) Bregs were also IL-10(high) expressing and further expanded when stimulated with semaphorin 3A. In sum we show that CD25(high)FoxP3(high) are an additional subtype of Bregs, involved in regulating SLE disease activity. Being IL-10 expressing, we may assume that they are one of the sources of increased serum IL-10 in SLE patients. Further studies are required in order to assess the relation between high serum IL-10 and CD25(high)FoxP3(high) Breg cells.
Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Zahava
Z
Vadasz
Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Regina
R
Peri
Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Nasren
N
Eiza
Rheumatology Unit, Bnai Zion Medical Center, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Gleb
G
Slobodin
B. Shine Rheumatology Unit, Rambam Health Care Campus, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Alexandra
A
Balbir-Gurman
Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine, Technion, 4940 Haifa, Israel.
Elias
E
Toubi
D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D040121:Semaphorin-3A / Q000378:metabolism; D012720:Severity of Illness Index; D055815:Young Adult
D018941:Antigens, CD19; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D040121:Semaphorin-3A; D016753:Interleukin-10