Expression of CCR2 on Monocytes and Macrophages in Chronically Inflamed Skin in Atopic Dermatitis and Psoriasis

Vestergaard, Christian; Just, Helle; Nielsen, Jane Baumgartner; Thestrup‐Pedersen, Kristian; Deleuran, Mette

doi:10.1080/00015550410034444

Cited by 80 publications

(59 citation statements)

References 25 publications

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“…S1B). C-C chemokine receptor type 2 (CCR2) plays a role in homing of macrophages to inflamed skin and is present on dermal γδT cells (3,26,27). IMQ-expanded LN Vγ4 + Vδ4 + cells expressed high levels of CCR2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

Ramírez‐Valle

Gray

Cyster

2015

Proc. Natl. Acad. Sci. U.S.A.

172

193

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Gamma delta (γδ) T cells represent a major IL-17 committed T-cell population (γδT17 cells) in the mouse dermis. Following exposure to the inflammatory agent imiquimod (IMQ) the Vγ4 + subset of γδT cells produce IL-17 in the skin and expand rapidly in draining lymph nodes (LNs). Local IMQ treatment in humans is known to exacerbate psoriasis skin lesion activity at distant sites. Whether expanded γδT17 cells sensitize distant sites to inflammation has been unknown. Here we show that expanded Vγ4 + γδT17 cells egress from LNs in a fingolimod (FTY720)-sensitive manner and use C-C chemokine receptor type 2 to accumulate in inflamed skin where they augment neutrophil recruitment and inflammation. They also travel to noninflamed skin and peripheral LNs and remain in elevated numbers at these distant sites for at least 3 mo. Sensitized mice show more rapid skin inflammation and greater proliferation and IL-17 production by Vγ4 + γδT cells upon imiquimod challenge. Transfer experiments confirm that memory-like Vγ4 + γδT17 cells respond more rapidly. Memory-like Vγ4 + γδT17 cells are distinguished by greater IL-1R1 expression and more proliferation in response to IL-1β. These findings establish that local skin inflammation leads to faster and stronger secondary responses to the same stimulus through longterm and systemic changes in the composition and properties of the dermal γδT-cell population.immunological memory | γδT cells | inflammation

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Section: Resultsmentioning

confidence: 99%

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

Ramírez‐Valle

Gray

Cyster

2015

Proc. Natl. Acad. Sci. U.S.A.

172

193

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“…Interestingly, the infiltrating macrophages presented both classical and alternative activation markers, as similarly described for human psoriasis (41). The pathogenic involvement of these subepidermally located macrophages, designated epithelium-lining macrophages, is largely unknown in human psoriasis (2)(3)(4)(5)42). Therefore, we used the PL/J CD18 hypo mouse model herein to study a potential role of macrophages in the pathogenesis of this chronic psoriasiform skin inflammation.…”

Section: Discussionmentioning

confidence: 99%

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

Wang¹

2006

Journal of Clinical Investigation

235

221

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The CD18 hypomorphic (CD18 hypo ) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of b 2 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 CD18 hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18 hypo mice and were identified as being an important source of TNF-a in vivo. Both depletion of macrophages and neutralization of TNF-a resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18 hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-a into the skin of healthy CD18 hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-a, 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-a.

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“…Macrophages contribute to psoriasis in 2 mouse models Infiltration of macrophages, especially around the epidermal/dermal interface, is a well-established feature of human psoriasis, but the contribution of these cells to psoriatic inflammation was previously unknown (14)(15)(16)(17)(18)(19). In this issue, Wang et al (20) and Stratis et al (12) address for the first time to our knowledge the importance of macrophages in mouse models of psoriasis.…”

Section: What Is To Blame In Psoriasis -T Cells or The Skin?mentioning

confidence: 98%

Misbehaving macrophages in the pathogenesis of psoriasis

Clark¹

2006

Journal of Clinical Investigation

135

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Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue of the JCI, 2 studies of very different mouse models of psoriasis both report that macrophages play a key role in inducing psoriasis-like skin disease. Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous inflammation. The debate that currently rages in the field is whether psoriasis is a disease of autoreactive T cells or whether it reflects an intrinsic defect within the skin -or both. However, these questions have proven difficult to dissect using molecular genetic tools. In the current studies, the authors have used 2 different animal models to address the role of macrophages in disease pathogenesis: Wang et al. use a mouse model in which inflammation is T cell dependent, whereas the model used by Stratis et al. is T cell independent (see the related articles beginning on pages 2105 and 2094, respectively). Strikingly, both groups report an important contribution by macrophages, implying that macrophages can contribute to both epithelial-based and T cell-mediated pathways of inflammation.

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Expression of CCR2 on Monocytes and Macrophages in Chronically Inflamed Skin in Atopic Dermatitis and Psoriasis

Cited by 80 publications

References 25 publications

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

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

Misbehaving macrophages in the pathogenesis of psoriasis

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Expression of CCR2 on Monocytes and Macrophages in Chronically Inflamed Skin in Atopic Dermatitis and Psoriasis

Cited by 80 publications

References 25 publications

Inflammation induces dermal Vγ4 + γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

Inflammation induces dermal Vγ4 + γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

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

Misbehaving macrophages in the pathogenesis of psoriasis

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Resources

About

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses

Inflammation induces dermal Vγ4 ⁺ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17–driven responses