Peptidoglycan recognition protein Pglyrp2 protects mice from psoriasis-like skin inflammation by promoting regulatory T cells and limiting Th17 responses.

Abstract

Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Psoriasis is a frequent inflammatory skin disease of unknown cause determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan recognition proteins (Pglyrps) are expressed in the skin, and we report in this article that they modulate sensitivity in an experimentally induced mouse model of psoriasis. We demonstrate that Pglyrp2(-/-) mice (but not Pglyrp3(-/-) and Pglyrp4(-/-) mice) are more sensitive to the development of 12-O-tetradecanoylphorbol 13-acetate-induced psoriasis-like inflammation, whereas Pglyrp1(-/-) mice are less sensitive. The mechanism underlying this increased sensitivity of Pglyrp2(-/-) mice to 12-O-tetradecanoylphorbol 13-acetate-induced psoriasis-like inflammation is reduced recruitment of regulatory T cells to the skin and enhanced production and activation of Th17 cells in the skin in Pglyrp2(-/-) mice, which results in more severe inflammation and keratinocyte proliferation. Thus, in wild type mice, Pglyrp2 limits overactivation of Th17 cells by promoting accumulation of regulatory T cells at the site of inflammation, which protects the skin from the exaggerated inflammatory response.

• Authors: Shin Yong Park, Dipika Gupta, Risa Hurwich, Chang H Kim, Roman Dziarski
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 187 Issue 11 Pg. 5813-23 (Dec 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 22048773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Carcinogens
• Proteins
• N-Acetylmuramoyl-L-alanine Amidase
• Pglyrp2 protein, mouse
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Carcinogens (toxicity)
• Cell Separation
• Disease Models, Animal
• Flow Cytometry
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• N-Acetylmuramoyl-L-alanine Amidase
• Proteins (immunology)
• Psoriasis (chemically induced, immunology)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes, Regulatory (immunology)
• Tetradecanoylphorbol Acetate (toxicity)
• Th17 Cells (immunology)