INVESTIGATIVE REPORT 325
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
CD1c + Blood Dendritic Cells in Atopic Dermatitis are Premature and Can Produce Disease-specific Chemokines
Anikó KAPITÁNY 1, 2 #, Gabriella BÉKE 1, 2 #, Georgina NAGY 1, 2, Quang Minh DOAN-XUAN 3, Zsolt BACSO 3, Krisztián GÁSPÁR 1, 2, Gábor BOROS 2, Zsolt DAJNOKI 1, 2, Tamás BÍRÓ 4, 5, Éva RAJNAVÖLGYI 4 and Andrea SZEGEDI 1, 2
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Division of Dermatological Allergology, Departments of 2 Dermatology, 3 Biophysics and Cell Biology and 4 Immunology, and 5 DE-MTA“ Lendület” Cellular Physiology Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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These authors contributed equally to this work.
Skin dendritic cells of patients with atopic dermatitis( AD) are well characterized, but less is known about their peripheral blood precursors. The aim of this study was to investigate the phenotypic features and chemokine production of myeloid pre-dendritic cells of patients with AD ex vivo and after stimulation with Staphylococcus enterotoxin B and thymic stromal lymphopoietin, representing an AD-like microenvironment. The expression of cell surface markers was measured by flow cytometry, while chemokine production was monitored with chemokine antibody array and confirmed by enzyme-linked immunoassays. AD pre-dendritic cells expressed higher levels of FcεRI and the maturation and activation markers tended to be altered. They produced both AD( CCL17 / 18 / 22) and maturation-related( CCL3 / 4 / 5) chemokines at higher level than controls. The production of CCL3 / 4 and CCL18 were significantly higher even without ADspecific stimulation, while the production of CCL17 and CCL22 were significantly higher only after stimulation. These results indicate that circulating AD pre-dendritic cells are premature and bear atopic characteristics even without tissue-specific stimulation, suggesting that their development is not only influenced by the skin microenvironment, but even earlier by the local milieu in the blood.
Key words: atopic dermatitis; dendritic cells; cell surface markers; chemokine.
Accepted Oct 3, 2016; Epub ahead of print Oct 4, 2016 Acta Derm Venereol 2017; 97: 325 – 331.
Corr: Andrea Szegedi, Division of Dermatological Allergology, Department of Dermatology, Faculty of Medicine, University of Debrecen, 98. Nagyerdei krt., HU-4032 Debrecen, Hungary. E-mail: aszegedi @ med. unideb. hu
Atopic dermatitis( AD) is a common inflammatory skin disease, in which both T cells and dendritic cells( DC) play crucial roles in the development of skin inflammation. AD is characterized by Th2- and Th22- type T-cell infiltration in both the initial and chronic phases( 1 – 6).
Beside T cells, DCs also represent the main participants in the pathogenesis of AD, since they contribute to inflammation both through their T-cell-polarizing capacity, and through direct cytokine and chemokine production. DCs serve as sentinels of the immune system and represent a heterogeneous family of myeloid cells. Skin myeloid DCs can be classified according to their tissue location and their surface molecule expression: Langerhans’ cells(( LCs) CD207 +( Langerin +), CD1a +, FcεRI +)) are the main cell types of the epidermis( 7), whereas dermal myeloid DCs( CD11c +, CD1c +, FcεRI +) can be found throughout the entire dermal compartment. Under inflammatory conditions, such as in AD skin, yet another cell type, the inflammatory dendritic epidermal cells(( IDECs) CD1a +, CD206 +)) develops( 8, 9).
In addition to monocytes, blood DCs are thought to be the precursors of DCs located in the skin and other tissues( 10, 11), and are often described as precursor DCs( pre- DCs). The precursor-progeny connection between CD1c + blood DCs and tissue CD1c + DCs is also supported by in vitro differentiation and gene expression analysis( 12). In AD, it has emerged that peripheral blood pre-DCs can serve as precursors, not just of dermal DCs, but also of skin inflammatory DCs( 11, 13).
In addition to their T-cell-polarizing cytokine production DCs are also important sources of chemokines. Several research groups have observed that in patients with AD skin DCs produce mainly CCL17, CCL18 and CCL22( 3, 14). CCL17 and CCL18 are considered as AD-related chemokines produced by skin myeloid DCs, which play a role in the trafficking of memory T cells and in regulating the Th2 immune response. CCL22, which is also an AD-related chemokine, is considered to be released mainly by plasmocytoid DCs( 3). On the other hand, little information on the chemokine production of blood DCs in AD is available.
Since the peripheral blood pre-DCs are poorly characterized in AD, we aimed to examine their characteristic features. In our previous study, AD pre-DCs showed differences in the production of T-cell-polarizing cytokines compared with pre-DCs from healthy controls( 15). The present study continues the detailed phenotypic characterization of these cells, focusing on their activation and maturation stage and their chemokine production, in order to determine whether they differ from myeloid pre-DCs of healthy individuals ex vivo and after stimulation with Staphylococcus enterotoxin B( SEB) and thymic stromal lymphopoietin( TSLP), which represent an AD-like microenvironment. Our results indicate that peripheral blood pre-DCs derived from patients with AD
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2540 Acta Derm Venereol 2017; 97: 325 – 331