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

Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andrew South, Olga Igoucheva

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

© 2017 The Authors 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.
Original languageEnglish
Pages (from-to)2298-2308
Number of pages11
JournalJournal of Investigative Dermatology
DOIs
Publication statusPublished - 1 Nov 2017

Fingerprint

Epidermolysis Bullosa
Blister
Stem cells
Chemokines
Cell Movement
Skin
Leukocytes
Stem Cells
Cytokines
Fluids
Junctional Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Assays
Ligands
T-cells
Lymphocytes
Immunophenotyping
Infiltration
Emigration and Immigration
Myeloid Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Alexeev, Vitali ; Salas-Alanis, Julio Cesar ; Palisson, Francis ; Mukhtarzada, Lila ; Fortuna, Giulio ; Uitto, Jouni ; South, Andrew ; 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. In: Journal of Investigative Dermatology. 2017 ; pp. 2298-2308.
@article{6308cc9dde5d4be593a4e3d5914120f9,
title = "Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration",
abstract = "{\circledC} 2017 The Authors 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.",
author = "Vitali Alexeev and Salas-Alanis, {Julio Cesar} and Francis Palisson and Lila Mukhtarzada and Giulio Fortuna and Jouni Uitto and Andrew South and Olga Igoucheva",
year = "2017",
month = "11",
day = "1",
doi = "10.1016/j.jid.2017.07.002",
language = "English",
pages = "2298--2308",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",

}

Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration. / Alexeev, Vitali; Salas-Alanis, Julio Cesar; Palisson, Francis; Mukhtarzada, Lila; Fortuna, Giulio; Uitto, Jouni; South, Andrew; Igoucheva, Olga.

In: Journal of Investigative Dermatology, 01.11.2017, p. 2298-2308.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration

AU - Alexeev, Vitali

AU - Salas-Alanis, Julio Cesar

AU - Palisson, Francis

AU - Mukhtarzada, Lila

AU - Fortuna, Giulio

AU - Uitto, Jouni

AU - South, Andrew

AU - Igoucheva, Olga

PY - 2017/11/1

Y1 - 2017/11/1

N2 - © 2017 The Authors 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.

AB - © 2017 The Authors 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.

U2 - 10.1016/j.jid.2017.07.002

DO - 10.1016/j.jid.2017.07.002

M3 - Article

SP - 2298

EP - 2308

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

ER -