Serum Th17 cytokines in leprosy: correlation with circulating CD4(+) CD25 (high)FoxP3 (+) T-regs cells, as well as down regulatory cytokines

• Published in: Archives of dermatological research Vol. 306; no. 9; pp. 793 - 801
• Main Authors: Attia, E A S, Abdallah, M, El-Khateeb, E, Saad, A A, Lotfi, R A, El-Shennawy, D
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2014
• Subjects: Adolescent; Adult; Aged; Biomarkers - blood; Case-Control Studies; Cytokines - blood; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Forkhead Transcription Factors - blood; Humans; Interleukin-10 - blood; Interleukin-17 - blood; Interleukin-2 Receptor alpha Subunit - blood; Interleukin-22; Interleukins - blood; Leprosy - blood; Leprosy - diagnosis; Leprosy - immunology; Leprosy - microbiology; Male; Middle Aged; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - microbiology; Th17 Cells - immunology; Th17 Cells - microbiology; Transforming Growth Factor beta - blood; Young Adult
• ISSN: 1432-069X
• DOI: 10.1007/s00403-014-1486-2

Leprosy is not only a bacteriological disease but also an immunological disease, in which T helper17 and CD4(+) CD25(high)FoxP3(+) regulatory T cells (T-regs), among others, may play a role. We aimed to evaluate serum levels of interleukin (IL)-17, IL-22 (Th17 cytokines), IL-10 and transforming growth factor (TGF)-β (down regulatory cytokines) in 43 untreated leprosy patients and 40 controls by enzyme-linked immunosorbent assay, and to assess circulating CD4(+) CD25(high)FoxP3(+)T-regs in patients using flow cytometry. Patients were grouped into tuberculoid, pure neural, borderline, lepromatous, type 1 reactional leprosy, and erythema nodosum leprosum. IL-10 and TGF-β were significantly higher in patients as compared to controls (p < 0.001), while IL-17, but not IL-22, was significantly lower (p < 0.001), with no significant difference comparing patients' subgroups. Significantly higher CD4(+) CD25(high)FoxP3(+)T-regs levels was detected in tuberculoid, type 1 reaction and pure neural leprosy, while the lowest levels in erythema nodosum leprosum (p < 0.001). TregsFoxP3 expression% was significantly lower in pure neural leprosy than other patients' subgroups (p < 0.05). T-regs/T-effs was lowest in erythema nodosum leprosum (p < 0.05). TGF-β correlated negatively with TregsFoxP3 expression% and T-effs% (p = 0.009 and 0.018 respectively). Leprosy is associated with defective IL-17 and overproduction of IL-10 and TGF-β. Tuberculoid, type 1 reaction and pure neural leprosy express significantly higher circulating T-regs, consistent with effector immune mechanisms activation, but with lower TregsFoxP3 expression (in pure neural leprosy). Erythema nodosum leprosum is characterized by deficient T-regs and increased TregsFoxP3 expression%. The present study pinpointed a potential role of Th17, CD4(+) CD25(high)FoxP3(+)T-regs, and probably CD4(+) CD25(+)IL-10(+) T regulatory cells 1 (Tr1), and Th3 in leprosy.