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

Abstract

SummaryBackgroundWe hypothesized that regulatory T cells (Tregs) are involved in the immunological abnormalities seen in patients with polymorphic light eruption (PLE).ObjectivesTo investigate the number and suppressive function of peripheral Tregs in patients with PLE compared with healthy controls.MethodsBlood 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.ResultsTregs 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.ConclusionsAn 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.

Narrowband UVB Phototherapy for Clinically Isolated Syndrome: A Trial to Deliver the Benefits of Vitamin D and Other UVB-Induced Molecules

“…Recent studies have also implicated UVR in the maintenance of a pool of B-regulatory cells in the periphery that can prevent an autoimmune attack on the CNS (55). Narrow band UVB irradiation can also increase peripheral T-regulatory cell numbers and their suppressive function in patients with polymorphic light eruption (56). …”

Cutaneous infiltration of plasmacytoid dendritic cells and T regulatory cells in skin lesions of polymorphic light eruption

“…We do know that PDCs cells can promote the generation, survival and expansion of Tregs through indoleamine 2,3 dioxygenase (IDO) and enhanced inducible costimulator ligand (ICOS‐L) and IDO expression by PDCs is binded to Tregs presence . According to that and recent results, we could assert that PLE patients may have a normal to higher number of PDCs and FOXP3+ CD4+ cells in front of an impaired suppressory function. The reason why Tregs in PLE patients have suboptimal suppressor capabilities is still unknown.…”

“…Previous studies have investigated Tregs distribution and activity in patients affected by PLE. Schweintzger and coll . demonstrated that medical photohardening with 311‐nm UVB increases the number of Tregs in the blood of PLE patients.…”

“…In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptive immunity in skin by their immunosuppressive capacity, induced by UVR. Expression of forkhead box (FOXP3) has been shown to reflect activity of Tregs, and it has been found to be suppressed in skin lesions and/or peripheral blood of patients affected by autoimmune diseases such as psoriasis, SLE, pemphigoid and PLE …”

Photodermatoses in skin of colour

“…Although UVR immunosuppression is a hallmark of normal skin, impaired immunosuppression has been postulated to result in a reaction to UVR‐induced neoantigens eventuating in the development of clinical lesions. Photohardening appears to improve this initial dysregulation by causing regulatory T‐cell proliferation that promotes immunotolerance …”