Original Article

Journal of Investigative Dermatology (1998) 111, 7–18; doi:10.1046/j.1523-1747.1998.00243.x

Generation and Cyclic Remodeling of the Hair Follicle Immune System in Mice

Ralf Paus, Carina van der Veen, Stefan Eichmüller1, Tobias Kopp, Evelin Hagen, Sven Müller-Röver and Udo Hofmann1

Department of Dermatology, Charité, Humboldt University, Berlin, Germany

Correspondence: Dr R. Paus, Department of Dermatology, Humboldt-Universität, Charité; Schumannstr. 20/21, D-10117 Berlin, Germany.

1Current address: Clinical Cooperation Unit for Dermato-Oncology (DKFZ), Department of Dermatology, University Hospital Mannheim, University of Heidelberg, D-68135 Mannheim, Germany.

Received 24 April 1997; Revised 19 February 1998; Accepted 26 February 1998.

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Abstract

In this immunohistomorphometric study, we have defined basic characteristics of the hair follicle (HF) immune system during follicle morphogenesis and cycling in C57BL/6 mice, in relation to the skin immune system. Langerhans cells and gammadelta T cell receptor immunoreactive lymphocytes were the predominant intraepithelial hematopoietic cells in neonatal mouse skin. After their numeric increase in the epidermis, these cells migrated into the HF, although only when follicle morphogenesis was almost completed. In contrast to Langerhans cells, gammadelta T cell receptor immunoreactive lymphocytes entered the HF only via the epidermis. Throughout HF morphogenesis and cycling, both cell types remained strikingly restricted to the distal outer root sheath. On extremely rare occasions, CD4+ or CD8+alphabetaTC were detected within the HF epithelium or the sebaceous gland. Major histocompatibility complex class II+, MAC-1+ cells of macrophage phenotype and numerous mast cells appeared very early on during HF development in the perifollicular dermis, and the percentage of degranulated mast cells significantly increased during the initiation of synchronized HF cycling (first catagen). During both depilation- and cyclosporine A-induced HF cycling, the numbers of intrafollicular Langerhans cells, gammadelta T cell receptor immunoreactive lymphocytes, and perifollicular dermal macrophages fluctuated significantly. Yet, no numeric increase of perifollicular macrophages was detectable during HF regression, questioning their proposed role in catagen induction. In summary, the HF immune system is generated fairly late during follicle development, shows striking differences to the extrafollicular skin immune system, and undergoes substantial hair cycle-associated remodeling. In addition, synchronized HF cycling is accompanied by profound alterations of the skin immune system.

Keywords:

CD4, CD8, E cadherin, gammadelta T cells, hair cycle, integrins, MAC-1, NLDC145

Abbreviations:

CsA-HC, cyclosporine-induced hair cycle; dep-HC, depilation-induced hair cycle; gammadeltaTCgammadelta, T cell receptor-positive lymphocytes; gammadeltaTCR+, gammadelta T-cell receptor immunoreactive; HF, hair follicle(s); HIS, hair follicle immune system; MAC, hmacrophages; MAC-1, CD11b (C3 bi receptor, = macrophage marker); MC, mast cells; MF, microscopic field; p.d., post-depilation; p.p., post-partum; SIS, skin immune system

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