Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin

doi:10.1016/j.bbrc.2009.01.071

Biochemical and Biophysical Research Communications

Volume 380, Issue 2, 6 March 2009, Pages 323-327

https://doi.org/10.1016/j.bbrc.2009.01.071 Get rights and content

Abstract

Interferon α-producing plasmacytoid dendritic cells (pDC) are crucial contributors to pro-inflammatory or tolerogenic immune responses and are important in autoimmune diseases such as psoriasis. pDC accumulate in the lesional skin of psoriasis patients, but are rarely found in the affected skin of patients with atopic dermatitis (AD). While homeostatic chemokine CXCL12 and inducible pro-inflammatory CXCR3 chemokine ligands may regulate pDC influx to psoriatic skin, the mechanism responsible for selective pDC recruitment in psoriasis vs. AD remains unknown. Circulating pDC from normal donors express a limited number of chemoattractant receptors, including CXCR3 and CMKLR1 (chemokine-like receptor 1). In this work, we demonstrate that circulating pDC from normal donors as well as psoriasis and AD patients express similar levels of CXCR3 and responded similarly in functional migration assays to CXCL10. We next found that blood pDC from normal, AD, and psoriasis patients express functional CMKLR1. In contrast to normal skin, however, lesional skin from psoriasis patients contains the active form of the CMKLR1 ligand chemerin. Furthermore, in affected skin from psoriatic patients the level of active chemerin was generally higher than in AD skin. Taken together, these results indicate that local generation of active chemerin may contribute to pDC recruitment to psoriatic skin.

Section snippets

Materials and methods

Chemoattractants. Recombinant human CXCL12 (SDF-1α) and CXCL10 (IP-10) were purchased from R&D Systems. StaphopainB (SspB)-activated chemerin was prepared as described previously [16].

Patients. All human studies were performed in accordance with guidelines established by Jagiellonian University Institutional Bioethics Committee under approved protocols. Declaration of Helsinki protocols were followed. A total of 46 psoriasis patients (age 34.4 ± 10 years; F:M, 23:23), 28 AD patients (age 25.9 ± 8.4

Results

In order to better understand the function of pDC in skin diseases, we characterized certain phenotypic and functional properties of pDC isolated from peripheral blood of psoriasis and AD patients. In agreement with previous reports, the percentage of circulating pDC was found to be higher in AD patients compared to healthy individuals, whereas we noted a decreased frequency of pDC in psoriasis patients [8], [11] (Fig. 1A). The differences in the frequency of circulating pDC may reflect

Discussion

pDC are a relatively newly defined subset of DC equipped with the unique functional capability to respond to viral or microbial nucleic acids by rapid and robust production of type I interferons (INFα/β). Interestingly, dysregulated production of INFα/β is strongly associated with autoimmune diseases such as SLE and psoriasis [6], [7], implicating activated pDC in these pathologic conditions. Therefore, pDC recruitment to the skin may be important to the development of autoimmune skin diseases.

Acknowledgments

We thank Drs. M. Dutka and J. Pułka for help with statistical analysis.

This work was supported in part by grants from the Polish Ministry of Scientific Research 2P04A07629 and SPUB3088 (to J.C.), by Fogarty International Research Collaborative Award R03TW007174-01 (to E.C.B. and J.C.) and by grant from EU 6th FP project SP6MTKD-CT-2006-042586 (to J.C.).

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Although it is unlikely that chemerin production in CKD is higher than that of healthy kidneys, human renal chemerin synthesis and its possible contribution to circulating chemerin concentration remain to be elucidated. Adipose tissue is considered to be the main source of circulating chemerin [6–59]. As a possible reason for increased serum chemerin levels in patients with renal dysfunction, the subcutaneous adipose tissue chemerin mRNA level of CKD patients was recently measured [54].
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Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgments

Curr. Opin. Immunol.

J. Allergy Clin. Immunol.

J. Allergy Clin. Immunol.

J. Invest. Dermatol.

J. Invest. Dermatol.

J. Biol. Chem.

J. Am. Acad. Dermatol.

Exp. Hematol.

IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors

Annu. Rev. Immunol.

Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules

Int. Immunol.

Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells

J. Immunol.

The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12

J. Exp. Med.

Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood

J. Immunol.