Format

Send to

Choose Destination
PLoS One. 2014 May 15;9(5):e94260. doi: 10.1371/journal.pone.0094260. eCollection 2014.

Abnormal interactions between perifollicular mast cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata.

Author information

1
Department of Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University of Münster, Münster, Germany.
2
Department of Dermatology, University of Lübeck, Lübeck, Germany.
3
Department of Internal Medicine and Medical Specialties, University "La Sapienza", Rome, Italy.
4
Department of Gynaecology and Obstetrics, University of Rostock, Rostock, Germany.
5
Department of Pharmacology, Clinical Pharmacology and Biochemistry, Chuvash State University Medical School, Cheboksary, Russia.
6
Laboratory for Skin Research, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Flieman Medical Center, Haifa, Israel.
7
Laboratory for Skin Research, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
8
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
9
Klinik Dr. Koslowski, Munich, Germany.
10
Department of Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University of Münster, Münster, Germany; Institute for Inflammation and Repair, University of Manchester, Manchester, United Kingdom.

Abstract

Alopecia areata (AA) is a CD8+ T-cell dependent autoimmune disease of the hair follicle (HF) in which the collapse of HF immune privilege (IP) plays a key role. Mast cells (MCs) are crucial immunomodulatory cells implicated in the regulation of T cell-dependent immunity, IP, and hair growth. Therefore, we explored the role of MCs in AA pathogenesis, focusing on MC interactions with CD8+ T-cells in vivo, in both human and mouse skin with AA lesions. Quantitative (immuno-)histomorphometry revealed that the number, degranulation and proliferation of perifollicular MCs are significantly increased in human AA lesions compared to healthy or non-lesional control skin, most prominently in subacute AA. In AA patients, perifollicular MCs showed decreased TGFβ1 and IL-10 but increased tryptase immunoreactivity, suggesting that MCs switch from an immuno-inhibitory to a pro-inflammatory phenotype. This concept was supported by a decreased number of IL-10+ and PD-L1+ MCs, while OX40L+, CD30L+, 4-1BBL+ or ICAM-1+ MCs were increased in AA. Lesional AA-HFs also displayed significantly more peri- and intrafollicular- CD8+ T-cells as well as more physical MC/CD8+ T-cell contacts than healthy or non-lesional human control skin. During the interaction with CD8+ T-cells, AA MCs prominently expressed MHC class I and OX40L, and sometimes 4-1BBL or ICAM-1, suggesting that MC may present autoantigens to CD8+ T-cells and/or co-stimulatory signals. Abnormal MC numbers, activities, and interactions with CD8+ T-cells were also seen in the grafted C3H/HeJ mouse model of AA and in a new humanized mouse model for AA. These phenomenological in vivo data suggest the novel AA pathobiology concept that perifollicular MCs are skewed towards pro-inflammatory activities that facilitate cross-talk with CD8+ T-cells in this disease, thus contributing to triggering HF-IP collapse in AA. If confirmed, MCs and their CD8+ T-cell interactions could become a promising new therapeutic target in the future management of AA.

PMID:
24832234
PMCID:
PMC4022513
DOI:
10.1371/journal.pone.0094260
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center