IL-22 Promotes Fibroblast-mediated Wound Repair in the Skin

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2012 Dec 11

PMID 23223145

Citations 83

Authors

Heather M McGee

Barbara A Schmidt

Carmen J Booth

George D Yancopoulos

David M Valenzuela

Andrew J Murphy

Sean Stevens

Richard A Flavell

Valerie Horsley

Affiliations

Soon will be listed here.

Abstract

Skin wound repair requires complex and highly coordinated interactions between keratinocytes, fibroblasts, and immune cells to restore the epidermal barrier and tissue architecture after acute injury. The cytokine IL-22 mediates unidirectional signaling from immune cells to epithelial cells during injury of peripheral tissues such as the liver and colon, where IL-22 causes epithelial cells to produce antibacterial proteins, express mucins, and enhance epithelial regeneration. In this study, we used IL-22(-/-) mice to investigate the in vivo role for IL-22 in acute skin wounding. We found that IL-22(-/-) mice displayed major defects in the skin's dermal compartment after full-thickness wounding. We also found that IL-22 signaling is active in fibroblasts, using in vitro assays with primary fibroblasts, and that IL-22 directs extracellular matrix (ECM) gene expression and myofibroblast differentiation both in vitro and in vivo. These data define roles of IL-22 beyond epithelial cross talk, and suggest that IL-22 has a previously unidentified role in skin repair by mediating interactions between immune cells and fibroblasts.

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References

Zenewicz L, Yancopoulos G, Valenzuela D, Murphy A, Stevens S, Flavell R . Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity. 2008; 29(6):947-57. PMC: 3269819. DOI: 10.1016/j.immuni.2008.11.003. View

Geboes L, Dumoutier L, Kelchtermans H, Schurgers E, Mitera T, Renauld J . Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum. 2009; 60(2):390-5. DOI: 10.1002/art.24220. View

Radaeva S, Sun R, Pan H, Hong F, Gao B . Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology. 2004; 39(5):1332-42. DOI: 10.1002/hep.20184. View

Goto M, Murakawa M, Kadoshima-Yamaoka K, Tanaka Y, Nagahira K, Fukuda Y . Murine NKT cells produce Th17 cytokine interleukin-22. Cell Immunol. 2008; 254(2):81-4. DOI: 10.1016/j.cellimm.2008.10.002. View

van Vliet E, Melis M, van Ewijk W . Monoclonal antibodies to stromal cell types of the mouse thymus. Eur J Immunol. 1984; 14(6):524-9. DOI: 10.1002/eji.1830140608. View

Kagami S, Rizzo H, Lee J, Koguchi Y, Blauvelt A . Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2009; 130(5):1373-83. PMC: 2892169. DOI: 10.1038/jid.2009.399. View

Kunz S, Wolk K, Witte E, Witte K, Doecke W, Volk H . Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol. 2006; 15(12):991-1004. DOI: 10.1111/j.1600-0625.2006.00516.x. View

Wolk K, Witte E, Wallace E, Docke W, Kunz S, Asadullah K . IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol. 2006; 36(5):1309-23. DOI: 10.1002/eji.200535503. View

Kim K, Kim H, Park J, Park J, Oh H, Woo Y . Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RANKL in human synovial fibroblasts. Arthritis Rheum. 2011; 64(4):1015-23. DOI: 10.1002/art.33446. View

10.

Dumoutier L, Leemans C, Lejeune D, Kotenko S, Renauld J . Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol. 2001; 167(7):3545-9. DOI: 10.4049/jimmunol.167.7.3545. View

11.

Zheng Y, Danilenko D, Valdez P, Kasman I, Eastham-Anderson J, Wu J . Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2006; 445(7128):648-51. DOI: 10.1038/nature05505. View

12.

Boniface K, Bernard F, Garcia M, Gurney A, Lecron J, Morel F . IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol. 2005; 174(6):3695-702. DOI: 10.4049/jimmunol.174.6.3695. View

13.

Liu S, Xu S, Blumbach K, Eastwood M, Denton C, Eckes B . Expression of integrin beta1 by fibroblasts is required for tissue repair in vivo. J Cell Sci. 2010; 123(Pt 21):3674-82. DOI: 10.1242/jcs.070672. View

14.

OConnor Jr W, Kamanaka M, Booth C, Town T, Nakae S, Iwakura Y . A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol. 2009; 10(6):603-9. PMC: 2709990. DOI: 10.1038/ni.1736. View

15.

Martin B, Hirota K, Cua D, Stockinger B, Veldhoen M . Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity. 2009; 31(2):321-30. DOI: 10.1016/j.immuni.2009.06.020. View

16.

Ma H, Liang S, Li J, Napierata L, Brown T, Benoit S . IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest. 2008; 118(2):597-607. PMC: 2200300. DOI: 10.1172/JCI33263. View

17.

Zenewicz L, Yancopoulos G, Valenzuela D, Murphy A, Karow M, Flavell R . Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity. 2007; 27(4):647-59. PMC: 2149911. DOI: 10.1016/j.immuni.2007.07.023. View

18.

Qiu C, Coutinho P, Frank S, Franke S, Law L, Martin P . Targeting connexin43 expression accelerates the rate of wound repair. Curr Biol. 2003; 13(19):1697-703. DOI: 10.1016/j.cub.2003.09.007. View

19.

Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa J, Renauld J . Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem. 2002; 277(37):33676-82. DOI: 10.1074/jbc.M204204200. View

20.

Sawicki G, Marcoux Y, Sarkhosh K, Tredget E, Ghahary A . Interaction of keratinocytes and fibroblasts modulates the expression of matrix metalloproteinases-2 and -9 and their inhibitors. Mol Cell Biochem. 2005; 269(1-2):209-16. DOI: 10.1007/s11010-005-3178-x. View