Activated macrophages are essential in a murine model for T cell–mediated chronic psoriasiform skin inflammation
Honglin Wang, … , Ingo Haase, Karin Scharffetter-Kochanek
Honglin Wang, … , Ingo Haase, Karin Scharffetter-Kochanek
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2105-2114. https://doi.org/10.1172/JCI27180.
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Research Article Dermatology

Activated macrophages are essential in a murine model for T cell–mediated chronic psoriasiform skin inflammation

Abstract

The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of β2 integrins (CD11/CD18) to only 2–16% of WT levels. Previously we found that this chronic psoriasiform skin inflammation also depends on the presence of CD4+ T cells. Herein we investigated the role of macrophages in this CD18hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice and were identified as being an important source of TNF-α in vivo. Both depletion of macrophages and neutralization of TNF-α resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-α into the skin of healthy CD18hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-α, but neither substance alone, resulted in the induction of psoriasiform skin inflammation around the injection sites with recruitment and activation of macrophages. Collectively, our data suggest that maintenance of psoriasiform skin inflammation critically depends on efficient recruitment and activation of macrophages with sufficient release of TNF-α.

Authors

Honglin Wang, Thorsten Peters, Daniel Kess, Anca Sindrilaru, Tsvetelina Oreshkova, Nico Van Rooijen, Athanasios Stratis, Andreas C. Renkl, Cord Sunderkötter, Meinhard Wlaschek, Ingo Haase, Karin Scharffetter-Kochanek

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Figure 2

Activated macrophages are an important source of TNF-α in the lesional skin of affectedCD18hypo mice.

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Activated macrophages are an important source of TNF-...
Double immunostaining with anti-mouse TNF-α and F4/80 mAb was performed on cryosections derived from the lesional skin of affected CD18hypo mice. (A) Macrophages (green) stained with F4/80–Alexa 488. (B) TNF-α (red) stained with TNF-α–Cy3. (C) Cell nuclei were stained with DAPI (blue). (D) Overlay depicting double staining of TNF-α and macrophages (yellow). (D–G) Both classically and alternatively activated macrophages were present in the lesional skin of CD18hypo mice. To characterize the activation pattern of macrophages infiltrating the skin of affected CD18hypo mice, cryosections from lesional skin were double stained with F4/80–Alexa 488 (green) and the markers of classically activated macrophages TNF-α–Cy3 (red) (D) and iNOS-Cy3 (red) (E) or with the markers of alternatively activated macrophages Dectin 1–Cy3 (red) (F) and Arginase 1–Cy3 (G). Overlay (yellow) represents double-positive cells, i.e., macrophages bearing specific activation markers. Cell nuclei were counterstained with DAPI (blue). Dotted lines indicate the border between epidermis and dermis. Original magnification, ×20.