TY - JOUR
T1 - Possible association of decreased serum CXCL14 levels with digital ulcers in patients with systemic sclerosis
AU - Fukui, Yuki
AU - Miyagawa, Takuya
AU - Hirabayashi, Megumi
AU - Yamashita, Takashi
AU - Saigusa, Ryosuke
AU - Miura, Shunsuke
AU - Nakamura, Kouki
AU - Yoshizaki, Ayumi
AU - Sato, Shinichi
AU - Asano, Yoshihide
N1 - Funding Information:
ACKNOWLEDGMENTS: This work was supported by a grant for Research on Intractable Diseases from The Ministry of Health, Labor and Welfare of Japan. The funder was not involved in study design, data collection, data analysis, manuscript preparation and publication decisions.
Publisher Copyright:
© 2019 Japanese Dermatological Association
PY - 2019/7
Y1 - 2019/7
N2 - CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.
AB - CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.
KW - CXCL14
KW - digital ulcers
KW - interstitial lung disease
KW - skin sclerosis
KW - systemic sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85065851217&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065851217&partnerID=8YFLogxK
U2 - 10.1111/1346-8138.14914
DO - 10.1111/1346-8138.14914
M3 - Article
C2 - 31087594
AN - SCOPUS:85065851217
SN - 0385-2407
VL - 46
SP - 584
EP - 589
JO - Journal of Dermatology
JF - Journal of Dermatology
IS - 7
ER -