The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury

Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A. Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R. Hata, Keiji Iwatsuki, Ce Tang, Richard L. Gallo

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.

Original languageEnglish
Pages (from-to)74-84
Number of pages11
JournalImmunity
Volume37
Issue number1
DOIs
Publication statusPublished - Jul 27 2012

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Keratinocytes
Skin
Wounds and Injuries
Psoriasis
Proteins
Interleukin-17
imiquimod
Interleukin-17 Receptors
Phosphatidylinositol 3-Kinase
Phosphotransferases
Cell Proliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Lai, Y., Li, D., Li, C., Muehleisen, B., Radek, K. A., Park, H. J., ... Gallo, R. L. (2012). The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury. Immunity, 37(1), 74-84. https://doi.org/10.1016/j.immuni.2012.04.010

The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury. / Lai, Yuping; Li, Dongqing; Li, Changwei; Muehleisen, Beda; Radek, Katherine A.; Park, Hyun Jeong; Jiang, Ziwei; Li, Zhiheng; Lei, Hu; Quan, Yanchun; Zhang, Tian; Wu, Yelin; Kotol, Paul; Morizane, Shin; Hata, Tissa R.; Iwatsuki, Keiji; Tang, Ce; Gallo, Richard L.

In: Immunity, Vol. 37, No. 1, 27.07.2012, p. 74-84.

Research output: Contribution to journalArticle

Lai, Y, Li, D, Li, C, Muehleisen, B, Radek, KA, Park, HJ, Jiang, Z, Li, Z, Lei, H, Quan, Y, Zhang, T, Wu, Y, Kotol, P, Morizane, S, Hata, TR, Iwatsuki, K, Tang, C & Gallo, RL 2012, 'The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury', Immunity, vol. 37, no. 1, pp. 74-84. https://doi.org/10.1016/j.immuni.2012.04.010
Lai, Yuping ; Li, Dongqing ; Li, Changwei ; Muehleisen, Beda ; Radek, Katherine A. ; Park, Hyun Jeong ; Jiang, Ziwei ; Li, Zhiheng ; Lei, Hu ; Quan, Yanchun ; Zhang, Tian ; Wu, Yelin ; Kotol, Paul ; Morizane, Shin ; Hata, Tissa R. ; Iwatsuki, Keiji ; Tang, Ce ; Gallo, Richard L. / The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury. In: Immunity. 2012 ; Vol. 37, No. 1. pp. 74-84.
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