Immunology of the Human Nail Apparatus: The Nail Matrix Is a Site of Relative Immune Privilege

Abstract

The nail apparatus is constantly exposed to environmental damage. It requires effective immune responses to combat infection, while avoiding the loss of nail production and regeneration by autoaggressive immunity. By immunohistology, we define here previously unknown characteristics of the normal human nail immune system (NIS). Compared with other regions of nail epithelium, human leukocyte antigen (HLA)-A/B/C expression is prominently down regulated on both keratinocytes and melanocytes of the proximal nail matrix (PNM), whereas HLA-G(+) is upregulated here. Together with the expression of macrophage migration inhibitory factor in PNM, this may serve to inhibit an natural killer (NK) cell attack on major histocompatibility complex (MHC) class Ia-negative PNM. PNM also displays strong immunoreactivity for potent, locally generated immunosuppressants such as transforming growth factor-beta1, alpha-melanocyte stimulating hormone, insulin-like growth factor-1, and adrenocorticotropic hormone, exhibits unusually few CD1a(+), CD4(+), or CD8(+), NK, and mast cells. Finally, MHC class II and CD 209 expression on CD1a(+) cells in and around the PNM is reduced, indicating diminished antigen-presenting capacity. Thus, the NIS strikingly differs from the skin immune system, but shows intriguing similarities to the hair follicle immune system, including the establishment of an area of relative immune privilege in the PNM. This nail immune privilege may offer a relative safeguard against autoimmunity. But, the localized intraepithelial defect of innate and adaptive immunity in the PNM revealed here also may impede effective anti-infection defense.

Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children

“…The nail matrix and hair follicle are known to be sites of immune privilege, with decreased HLA-A, B and C expression on keratinocytes and melanocytes as well as decreased MHC class II expression of epidermal antigen presenting cells. [5][6][7] Downregulation of antigen recognition and T-cell activation decreases the likelihood of cGVHD at these sites. Thus adnexal involvement may indicate more profound immune dysregulation and predict treatment-refractory disease.…”

Lymphocytes, neuropeptides, and genes involved in alopecia areata

“…This is regrettable, because AA provides an excellent opportunity to study the roles of immunogenetics, immune privilege collapse, and neuroimmune-endocrine factors in a highly instructive and exquisitely accessible human model system of organ-specific autoimmunity (2,3). The existence of excellent related animal models of this condition (4-6) and human hair follicle organ culture systems (7), which can instructively complement in vivo research in the human system, make AA very attractive as a model system for the study of autoimmunity.…”

Recurrent Paronychia as a Presenting Manifestation of Pemphigus Vulgaris: A Case Report

“…It manifests as chronic paronychia, onychomadesis, Beau's lines, trachyonychia, onycholysis, subungual hemorrhage, nail plate discoloration, pitting, onychoschizia, and nail dystrophy [6,7,8,9,10,11,12,13,14,15,16,17,18,19]. Pseudopyogenic granuloma of the proximal or lateral nail fold can also be seen, and it has been reported to be the first symptom of a relapse of the disease [20].…”

“…This area of relative “immune privilege” in the proximal nail matrix constitutes a safeguard against autoimmunity. The number and function of antigen-presenting cells are substantially lower in the nail immune system than in the cutaneous or mucosal epidermis [5,19]. Also, there is a downregulation of major histocompatibility class II and CD209 expression by Langerhans cells in the proximal nail matrix with reduced function and/or number of natural killer and mast cells around the human nail apparatus [19].…”