title: CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling.
abstract: 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.
authors: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors: Yohei
authors: Y
authors: Iwata
authors: Ayumi
authors: A
authors: Yoshizaki
authors: Kazuhiro
authors: K
authors: Komura
authors: Kazuhiro
authors: K
authors: Shimizu
authors: Fumihide
authors: F
authors: Ogawa
authors: Toshihide
authors: T
authors: Hara
authors: Eiji
authors: E
authors: Muroi
authors: Sangjae
authors: S
authors: Bae
authors: Motoi
authors: M
authors: Takenaka
authors: Toru
authors: T
authors: Yukami
authors: Minoru
authors: M
authors: Hasegawa
authors: Manabu
authors: M
authors: Fujimoto
authors: Yasushi
authors: Y
authors: Tomita
authors: Thomas F
authors: TF
authors: Tedder
authors: Shinichi
authors: S
authors: Sato
mesh_terms: 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*
chemical_list: D018941:Antigens, CD19; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006820:Hyaluronic Acid