Pro-inflammatory chemokines and cytokines dominate the blister fluid molecular signature in patients with epidermolysis bullosa and affect leukocyte and stem cell migration
Date
2017
Type:
Artículo
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11
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ORCID:
Journal Title
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Volume Title
Publisher
Elsevier
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Abstract
Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of
chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve
wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin
lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients
affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1,
CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro
migration assays demonstrated the preferential recruitment of CCR4+
lymphocytes and CXCR1+
,
CXCR2+
, and CCR2+ myeloid cells toward EB-derived blister fluids. Immunophenotyping of skininfiltrating
leukocytes confirmed substantial infiltration of EB-affected skin with resting (CD45RA+
)
and activated (CD45RO+
) T cells and CXCR2+ CD11b+
cells, many of which were identified as
CD16b+ neutrophils. Our studies also showed that abundance of CXCR2 ligand in blister fluids also
creates a favorable milieu for the recruitment of the CXCR2+
stem cells, as validated by in vitro and
in-matrix migration assays. Collectively, this study identified several chemotactic pathways that
control the recruitment of leukocytes to the EB-associated skin lesions. These chemotactic axes
could be explored for the refinement of the cutaneous homing of the therapeutic stem cells.
Description
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Citation
Alexeev V, Salas-Alanis JC, Palisson F, Mukhtarzada L, Fortuna G, Uitto J, South A, Igoucheva O. Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration. J Invest Dermatol. 2017 Nov;137(11):2298-2308.
Keywords
Chemokines, Epidermolysis Bullosa, Receptors, CXCR, Cytokines