CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling.
Immune cells are critical to the wound-healing process, through both cytokine and growth factor secretion. Although previous studies have revealed that B cells are present within wound tissue, little is known about the role of B cells in wound healing. To clarify this, we investigated cutaneous wound healing in mice either lacking or overexpressing CD19, a critical positive-response regulator of B cells. CD19 deficiency inhibited wound healing, infiltration of neutrophils and macrophages, and cytokine expression, including basic and acidic fibroblast growth factor, interleukin-6, platelet-derived growth factor, and transforming growth factor-beta. By contrast, CD19 overexpression enhanced wound healing and cytokine expression. Hyaluronan (HA), an endogenous ligand for toll-like receptor (TLR)-4, stimulated B cells, which infiltrates into wounds to produce interleukin-6 and transforming growth factor-beta through TLR4 in a CD19-dependent manner. CD19 expression regulated TLR4 signaling through p38 activation. HA accumulation was increased in injured skin tissue relative to normal skin, and exogenous application of HA promoted wound repair in wild-type but not CD19-deficient mice, suggesting that the beneficial effects of HA to the wound-healing process are CD19-dependent. Collectively, these results suggest that increased HA accumulation in injured skin induces cytokine production by stimulating B cells through TLR4 in a CD19-dependent manner. Thus, this study is the first to reveal a critical role of B cells and novel mechanisms in wound healing.
Iwata
Yohei
Y
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Yoshizaki
Ayumi
A
Komura
Kazuhiro
K
Shimizu
Kazuhiro
K
Ogawa
Fumihide
F
Hara
Toshihide
T
Muroi
Eiji
E
Bae
Sangjae
S
Takenaka
Motoi
M
Yukami
Toru
T
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Tomita
Yasushi
Y
Tedder
Thomas F
TF
Sato
Shinichi
S
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006820:Hyaluronic Acid / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014945:Wound Healing / Q000276:immunology*
D018941:Antigens, CD19; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006820:Hyaluronic Acid