CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling

Yohei Iwata, Ayumi Yoshizaki, Kazuhiro Komura, Kazuhiro Shimizu, Fumihide Ogawa, Toshihide Hara, Eiji Muroi, Sangjae Bae, Motoi Takenaka, Toru Yukami, Minoru Hasegawa, Manabu Fujimoto, Yasushi Tomita, Thomas F. Tedder, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


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-β. 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-β 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.

Original languageEnglish
Pages (from-to)649-660
Number of pages12
JournalAmerican Journal of Pathology
Issue number2
Publication statusPublished - 08-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine


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