Levels and function of regulatory T cells in patients with polymorphic light eruption: relation to photohardening

• Published in: British journal of dermatology (1951) Vol. 173; no. 2; pp. 519 - 526
• Main Authors: Schweintzger, N., Gruber-Wackernagel, A., Reginato, E., Bambach, I., Quehenberger, F., Byrne, S.N., Wolf, P.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.08.2015; Oxford University Press; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; CD25 antigen; CD4 antigen; Cell proliferation; Cell Proliferation - physiology; Effector cells; Female; Flow cytometry; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene expression; Humans; Immune system; Immunoregulation; Light therapy; Lymphocytes; Lymphocytes T; Male; Middle Aged; mRNA; Original; Photobiology; Photosensitivity Disorders - immunology; Photosensitivity Disorders - metabolism; Photosensitivity Disorders - radiotherapy; Phototherapy; Seasons; Skin eruptions; Statistical analysis; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - physiology; Ultraviolet Therapy - methods; Up-Regulation - physiology; Young Adult
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.13930

Summary Background We hypothesized that regulatory T cells (Tregs) are involved in the immunological abnormalities seen in patients with polymorphic light eruption (PLE). Objectives To investigate the number and suppressive function of peripheral Tregs in patients with PLE compared with healthy controls. Methods Blood sampling was done in 30 patients with PLE [seeking or not seeking 311‐nm ultraviolet (UV)B photohardening] as well as 19 healthy controls at two time points: TP1, March to June (before phototherapy); and TP2, May to August (after phototherapy). We compared the number of CD4+CD25highCD127−FoxP3+ Tregs by flow cytometry and their function by assessing FoxP3 mRNA levels and effector T cell/Treg suppression assays. Results Tregs isolated from healthy controls significantly suppressed the proliferation of effector T cells at TP1 by 68% (P = 0·0156). In contrast, Tregs from patients with PLE entirely lacked the capacity to suppress effector T‐cell proliferation at that time point. The medical photohardening seen in 23 patients with PLE resulted in a significant increase in the median percentage of circulating Tregs [both as a proportion of all lymphocytes; 65 6% increase (P = 0·0049), and as a proportion of CD4+ T cells; 32.5% increase (P = 0·0049)]. This was accompanied by an increase in the expression of FoxP3 mRNA (P = 0·0083) and relative immunosuppressive function of Tregs (P = 0·083) comparing the two time points in representative subsets of patients with healthy controls tested. Seven patients with PLE not receiving 311‐nm UVB also exhibited an increase in the number of Tregs but this was not statistically significant. No significant differences in Treg numbers were observed in healthy subjects between the two time points. Conclusions An impaired Treg function is likely to play a role in PLE pathogenesis. A UV‐induced increase in the number of Tregs (either naturally or therapeutically) may be a compensatory mechanism by which the immune system counteracts the susceptibility to PLE. What's already known about this topic? Patients with polymorphic light eruption (PLE) display immunological abnormalities. Previous studies have shown that they are resistant to the immune suppressive effects of sunlight. What does this study add? We found that the number and suppressive function of regulatory T cells (Tregs) are crucial in the pathogenesis of PLE. An increase in Treg levels (after photohardening) might be a compensatory mechanism by which the immune system intends to counteract the susceptibility to PLE formation.