TY - JOUR
T1 - Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells
AU - Ou, Lingling
AU - Shi, Ying
AU - Dong, Wenqi
AU - Liu, Chunming
AU - Schmidt, Thomas J.
AU - Nagarkatti, Prakash
AU - Nagarkatti, Mitzi
AU - Fan, Daping
AU - Ai, Walden
N1 - Publisher Copyright:
© 2015 The Society for Investigative Dermatology.
PY - 2015/5/22
Y1 - 2015/5/22
N2 - Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.
AB - Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.
UR - http://www.scopus.com/inward/record.url?scp=84928421104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928421104&partnerID=8YFLogxK
U2 - 10.1038/jid.2015.3
DO - 10.1038/jid.2015.3
M3 - Article
C2 - 25581502
AN - SCOPUS:84928421104
SN - 0022-202X
VL - 135
SP - 1425
EP - 1434
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -