The mast cell/S1P axis is not linked to pre-lesional male skin remodeling in a mouse model of eczema

Ross M. Tanis; Piper A. Wedman-Robida; Alena P. Chumanevich; John W. Fuseler; Carole A. Oskeritzian; Ross M. Tanis; Piper A. Wedman-Robida; Alena P. Chumanevich; John W. Fuseler; Carole A. Oskeritzian

doi:10.3934/Allergy.2021012

AIMS Allergy and Immunology

2021, Volume 5, Issue 3: 160-174. doi: 10.3934/Allergy.2021012

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Research article

The mast cell/S1P axis is not linked to pre-lesional male skin remodeling in a mouse model of eczema

1.
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
2.
Department of Internal Medicine, Loyola University Medical Center, 2160 South 1st Avenue, Maywood, IL 60153, USA
3.
Department of Natural Science, Northwestern Oklahoma State University, Science Building 100-D, 709 Oklahoma Boulevard, Alva, OK 73717, USA
† These two authors contributed equally.

Received: 25 March 2021 Accepted: 25 May 2021 Published: 28 May 2021

Atopic dermatitis (AD, eczema) is an inflammatory skin condition whose histopathology involves remodeling. Few preclinical AD studies are performed using male mice. The histopathological mechanisms underlying AD development were investigated here in male mice at a pre-lesional stage using a human AD-like mouse model. Hypodermal cellular infiltration without thickening of skin layers was observed after one epicutaneous exposure to antigen ovalbumin (OVA), compared to controls. In contrast to our previous report using female mice, OVA treatment did not activate skin mast cells (MC) or elevate sphingosine-1-phosphate (S1P) levels while increasing systemic but not local levels of CCL2, CCL3 and CCL5 chemokines. In contrast to the pathogenic AD mechanisms we recently uncovered in female, S1P-mediated skin MC activation with subsequent local chemokine production is not observed in male mice, supporting sex differences in pre-lesional stages of AD. We are proposing that differential involvement of the MC/S1P axis in early pathogenic skin changes contributes to the well documented yet still incompletely understood sex-dimorphic susceptibility to AD in humans.
- pathogenesis,
- mast cells,
- sphingosine-1-phosphate,
- chemokines,
- animal models,
- eczema
Citation: Ross M. Tanis, Piper A. Wedman-Robida, Alena P. Chumanevich, John W. Fuseler, Carole A. Oskeritzian. The mast cell/S1P axis is not linked to pre-lesional male skin remodeling in a mouse model of eczema[J]. AIMS Allergy and Immunology, 2021, 5(3): 160-174. doi: 10.3934/Allergy.2021012

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Abstract

Atopic dermatitis (AD, eczema) is an inflammatory skin condition whose histopathology involves remodeling. Few preclinical AD studies are performed using male mice. The histopathological mechanisms underlying AD development were investigated here in male mice at a pre-lesional stage using a human AD-like mouse model. Hypodermal cellular infiltration without thickening of skin layers was observed after one epicutaneous exposure to antigen ovalbumin (OVA), compared to controls. In contrast to our previous report using female mice, OVA treatment did not activate skin mast cells (MC) or elevate sphingosine-1-phosphate (S1P) levels while increasing systemic but not local levels of CCL2, CCL3 and CCL5 chemokines. In contrast to the pathogenic AD mechanisms we recently uncovered in female, S1P-mediated skin MC activation with subsequent local chemokine production is not observed in male mice, supporting sex differences in pre-lesional stages of AD. We are proposing that differential involvement of the MC/S1P axis in early pathogenic skin changes contributes to the well documented yet still incompletely understood sex-dimorphic susceptibility to AD in humans.

Abbreviations

atopic dermatitis

OVA

ovalbumin

MCs

mast cells

S1P

sphingosine-1-phosphate

blood vessels

Acknowledgments

We thank VCU Lipidomics/Metabolomics Core for lipid determinations, which is supported by the National Institutes of Health (NIH)/NCI Cancer Center Support grant P30 CA016059 to the VCU Massey Cancer Center and by a shared resource grant S10RR031535. We thank Ahmed Aladami for technical assistance. This work was supported by the National Institute of Allergy and Infectious Diseases/NIH R01 AI095494, the National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH R21 AR067996 and a National Institute of General Medical Sciences/NIH Bioinformatics Pilot Project P20 GM103499 to CAO.

Conflict of interest

All authors declare no conflicts of interest in this paper.

Author contributions

Conception and study design: PAWR and CAO; Development of methodology: PAWR, APC, RMT, JWF and CAO; Acquisition of data: RMT, PAWR, APC, JWF; Analysis and interpretation of data: RWT, PAWR, APC, JWF, CAO; Technical support: APC, JWF; Writing, review and/or revision of the manuscript: RWT, PAWR, APC, JWF, CAO.

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