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