CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow-derived keratinocytes.
Recent studies have suggested that bone marrow (BM) cells transdifferentiate to regenerate a variety of cellular lineages. Due to the relatively small population of BM-derived cells in each organ, it is still controversial whether these BM-derived cells are really present in sufficient numbers for effective function. Conversely, it is speculated that chemokine/chemokine receptor interactions mediate this migration of the tissue-specific precursor cells from BM into the target tissue. Here, we show that cutaneous T-cell attracting chemokine (CTACK)/CCL27 is the major regulator involved in the migration of keratinocyte precursor cells from BM into skin. By screening various chemokine expression patterns, we demonstrated that CTACK is constitutively expressed in normal skin and upregulated in wounds and that approximately 20% of CD34(+) BM cells expressed CCR10, the ligand for CTACK. Intradermal injection of CTACK/CCL27 into the periphery of skin wounds significantly enhanced BM-derived keratinocyte (BMDK) migration, and CTACK/CCL27 neutralizing antibody inhibited this BMDK migration. Furthermore, increased BMDK migration caused by CTACK/CCL27 significantly accelerated the wound-healing process without any influence over either angiogenesis or keratinocyte proliferation. These results provide direct evidence that recruitment of BM keratinocyte precursor cells to the skin is regulated by specific chemokine/chemokine receptor interactions, making possible the development of new regenerative therapeutic strategies.
Inokuma
Daisuke
D
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Abe
Riichiro
R
Fujita
Yasuyuki
Y
Sasaki
Mikako
M
Shibaki
Akihiko
A
Nakamura
Hideki
H
McMillan
James R
JR
Shimizu
Tadamichi
T
Shimizu
Hiroshi
H
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054421:Chemokine CCL21; D054425:Chemokine CCL27; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D012879:Skin Physiological Phenomena; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D018952:Antigens, CD34; C514936:CXCR4 protein, mouse; C515479:Ccl21c protein, mouse; C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D054425:Chemokine CCL27; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine