Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea.
BACKGROUND
Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases.


OBJECTIVE
To investigate the presence of Tregs and their immunomodulatory cytokines, transforming growth factor (TGF)-beta and interleukin (IL)-10, in patients with SSc and morphoea.


METHODS
Fifteen patients with SSc and 15 with morphoea were enrolled. Immunohistochemistry was applied to identify FoxP3+ (forkhead/winged helix transcription factor) Tregs, TGF-beta+ cells and IL-10+ cells in the skin, cytofluorometry to detect CD4+CD25+FoxP3+ Tregs in the blood, and enzyme-linked immunosorbent assays to analyse TGF-beta and IL-10 serum levels.


RESULTS
Fewer FoxP3+ Tregs and TGF-beta+ and IL-10+ cells were found in the skin of patients with scleroderma than in controls. Similarly, there were reduced TGF-beta and IL-10 serum levels and fewer circulating CD4+CD25brightFoxP3+ cells in patients with SSc or morphoea, than in controls.


CONCLUSIONS
The quantitative reduction of Tregs, together with that of TGF-beta and IL-10 serum levels, may be responsible for the loss of tolerance observed in both SSc and morphoea.
Antiga
E
E
Department of Dermatological Sciences, University of Florence, Via della Pergola 58/60, 50121 Florence, Italy.
Quaglino
P
P
Bellandi
S
S
Volpi
W
W
Del Bianco
E
E
Comessatti
A
A
Osella-Abate
S
S
De Simone
C
C
Marzano
A
A
Bernengo
M G
MG
Fabbri
P
P
Caproni
M
M
D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012594:Scleroderma, Localized / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000097:blood
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10