Selective Elimination of NG2-Expressing Hair Follicle Stem Cells Exacerbates the Sensitization Phase of Contact Dermatitis in a Transgenic Rat Model.

Yasuhisa Tamura,Yosky Kataoka,Asami Eguchi,Kumi Takata

doi:10.3390/ijms21186922

Yasuhisa Tamura, Yosky Kataoka + Show 2 more

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https://doi.org/10.3390/ijms21186922

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Abstract

The hair cycle consists of three different phases: anagen (growth), catagen (regression), and telogen (resting). During the anagen phase, hair follicle stem cells (HFSCs) in the bulge and the secondary hair germ proliferate and generate the outer and inner root sheath cells and the hair shafts. We previously identified NG2-immunoreactive (NG2+) cells as HFSCs in both regions of the hair follicles. Recently, the interaction between the hair cycle and the cutaneous immune system has been re-examined under physiological and pathological conditions. However, the roles of NG2+ HFSCs in the skin’s immune system remain completely elucidated. In the present study, we investigated whether the elimination of NG2+ HFSCs affects the induction of allergic contact dermatitis, using a herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene system. When the GCV solution was applied to the skin of NG2-HSVtk transgenic (Tg) rats during the depilation-induced anagen phase, NG2+ HFSCs in the Tg rat skin induced apoptotic cell death. Under exposure of a hapten, the selective ablation of NG2+ HFSCs during the anagen phase aggravated the sensitization phase of allergic contact dermatitis. These findings suggest that NG2+ HFSCs and their progeny have immunosuppressive abilities during the anagen phase.

Highlights

The hair cycle in mammals consists of three distinct stages: anagen, catagen, and telogen [1,2]
We investigated the effects of the selective ablation of NG2-expressing hair follicle stem cells (HFSCs) on dinitrofluorobenzene (DNFB)-induced contact dermatitis in a rat model, using the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV)
On day nine (Figure 6C, Table 2; n = 4). These results demonstrated that the selective ablation of NG2expressing HFSCs during the anagen phase provoked the exacerbation of contact dermatitis following exposure to DNFB, whereas only the topical application of 0.5% DNFB elicited redness, but never induced more severe symptoms, such as dry, cracked, and scaly skin, in the presence of NG2+

Summary

Introduction

The hair cycle in mammals consists of three distinct stages: anagen (growing phase), catagen (regressing phase), and telogen (resting phase) [1,2]. Hair follicle stem cells (HFSCs) in the bulge region and secondary hair germ (sHG) cells proliferate and produce their progenies, including outer root sheath cells, inner root sheath cells, and hair shafts [3,4]. HFSCs in the bulge are composed of heterogeneous cell populations, including CD34+ Lgr5– cells and CD34+ Lgr5+. The sHG cells are immunopositive for Lgr, but not CD34. We recently reported that all cell populations in the bulge and sHG are immunoreactive for NG2, known as chondroitin sulfate proteoglycan 4 (CSPG4), and that the NG2-immunopositive (NG2+) cells in both regions of the hair follicles have proliferative ability [7]. The activation of HFSCs is known to be regulated by macrophages [8,9,10] and regulatory

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