The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury

Lai et al., 2012. Immunity, 37(1), 74-84.

Speaker: Pei-Chi Chen (陳佩琪)                                   Time: 15:00~16:00, Nov. 28, 2012

Commentator: Dr. Ching-Hao Teng (鄧景浩 老師)    Location: Room 601

Abstract:

A well-controlled balance between keratinocyte proliferation and differentiation is an important component of wound healing, while intrinsic alterations of keratinocytes would induce psoriasis. Psoriasis is a chronic inflammatory skin disease triggered by Th1- and Th17-cell mediated immune responses augmenting keratinocyte proliferation. Several researches have demonstrated that psoriatic keratinocytes are a rich source of antimicrobial peptides. In addition to their antimicrobial activity, kerotinocytes also possess chemotactic function and the ability to alter immune cell behavior. However the element that drives epithelial keratinocyte proliferation remains unknown. In this study, Lai et al. recognized antimicrobial protein REG3A (regenerating islet-derived protein 3-alpha) as a potential link between cells that induces the production of IL-17A and thehyperproliferation response of psoriatic keratinocytes. It is shown that REG3A or RegIIIγ (mouse homolog of human REG3A) protein are overexpressed in wound repair and in both human tissue and imiquimod mouse model psoriatic lesional skin. By using in vitro NEHK wound and in vivowound healing, they found that REG3A could increase kerationcyte proliferation and inhibit differentiation, significantly accelerating wound re-epithelialization. To better understand the regulatory mechanism, they treated NHEKs with a panel of proinflammatory cytokines, demonstrating that IL-17A induces the expression of REG3A via IL-17A receptor activation in response to IL-22 stimulation. Furthermore, it was found that REG3A regulates keratinocyte proliferation via EXTL3-PI3K-AKT signaling pathway. In conclusion, this study illustrated that REG3A, a secreted intestinal antimicrobial protein, induced by IL-17A may conduct keratinocyte proliferation. This finding signified REG3A as a therapeutic targeting candidate in psoriasis and skin injury.

References:

1.         Nestle, F.O., Kaplan, D.H., and Barker, J. (2009). Psoriasis. New England Journal of Medicine 361, 496-509.

2.         Albanesi, C., De Pita, O., and Girolomoni, G. (2007). Resident skin cells in psoriasis: a special look at the pathogenetic functions of keratinocytes. Clinics in dermatology 25, 581-588.