Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration.

Authors

Vitali Alexeev, Thomas Jefferson UniversityFollow
Julio Cesar Salas-Alanis, University of Monterrey
Francis Palisson, Clínica Alemana Universidad del Desarrollo
Lila Mukhtarzada, Thomas Jefferson UniversityFollow
Giulio Fortuna, Louisiana State University School of Dentistry
Jouni Uitto, Thomas Jefferson UniversityFollow
Andrew P. South, Thomas Jefferson UniversityFollow
Olga Igoucheva, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

11-1-2017

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Journal of Investigative Dermatology, Volume 137, Issue 11, November 2017, Pages 2298-2308.

The published version is available at https://doi.org/10.1016/j.jid.2017.07.002. Copyright © Alexeev et al.

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 skin-infiltrating 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. © 2017 The Authors

Recommended Citation

Alexeev, Vitali; Salas-Alanis, Julio Cesar; Palisson, Francis; Mukhtarzada, Lila; Fortuna, Giulio; Uitto, Jouni; South, Andrew P.; and Igoucheva, Olga, "Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration." (2017). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 103.
https://jdc.jefferson.edu/dcbfp/103

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

28736230

Language

English