Decreased expression of Runx1 and lowered proportion of Foxp3⁺ CD25⁺ CD4⁺ regulatory T cells in systemic sclerosis.
OBJECTIVE
To investigate the role of Foxp3(+) CD25(+) CD4(+) regulatory T cells (Treg) and their transcription factor, Runt-related transcription factor 1 (Runx1), in the pathogenesis and development of systemic sclerosis (SSc).


METHODS
We collected 23 blood samples from patients with SSc including 19 females and 4 males, 11 early-stage cases within 3 years from onset and 12 late-stage cases and 22 samples from age-matched healthy subjects (HS). Total CD4(+) T cells were assessed for the expression of Treg-related markers, CD25 and CD127, on their surface and intracellular Foxp3 using flow cytometry. Relative expression of Runx1 mRNA in magnetically purified Treg was analyzed using real-time PCR.


RESULTS
Proportion of Foxp3(+) cells in total CD4(+) T cells was decreased in patients with either early- or late-stage SSc compared with that in HS, and Runx1 mRNA expression in purified Treg was lower in patients with SSc than in HS. Runx1 mRNA expression level was related to the frequency of Treg in SSc.


CONCLUSIONS
This is the first report on Runx1 expression in Treg of a human autoimmune disease. Low expression of Runx1 along with reduced proportion of Treg in CD4(+) T cells may be associated with development of SSc even in early disease.
Department of Medicine II, Hokkaido University Graduate School of Medicine , Sapporo , Japan.
Hiroshi
H
Kataoka
Shinsuke
S
Yasuda
Shinji
S
Fukaya
Kenji
K
Oku
Tetsuya
T
Horita
Tatsuya
T
Atsumi
Takao
T
Koike
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D050676:Core Binding Factor Alpha 2 Subunit; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; C493728:RUNX1 protein, human
Foxp3; Regulatory T cell; Runx1; Systemic sclerosis