Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

Abstract

Immune privilege (IP) is important in maintaining ocular health. Understanding the mechanism underlying this dynamic state would assist in treating inflammatory eye diseases. Despite substantial progress in defining eye IP mechanisms, because of the scarcity of human ocular tissue for research purposes, most of what we know about ocular IP is based on rodent models (of unclear relevance to human eye immunology) and on cultured human eye-derived cells that cannot faithfully mirror the complex cell-tissue interactions that underlie normal human ocular IP in situ. Therefore, accessible, instructive, and clinically relevant human in vitro models are needed for exploring the general principles of why and how IP collapses under clinically relevant experimental conditions and how it can be protected or even restored therapeutically. Among the few human IP sites, the easily accessible and abundantly available hair follicle (HF) may offer one such surrogate model. There are excellent human HF organ culture systems for the study of HF IP in situ that instructively complement in vivo autoimmunity research in the human system. In this article, we delineate that the human eye and HF, despite their obvious differences, share key molecular and cellular mechanisms for maintaining IP. We argue that, therefore, human scalp HFs can provide an unconventional, but highly instructive, accessible, easily manipulated, and clinically relevant preclinical model for selected aspects of ocular IP. This essay is an attempt to encourage professional eye researchers to turn their attention, with appropriate caveats, to this candidate surrogate model for ocular IP in the human system.

Calcitonin gene‐related peptide (CGRP) may award relative protection from interferon‐γ‐induced collapse of human hair follicle immune privilege

“…In the aqueous humour, where CGRP is a constitutive neuropeptide, its immunoinhibitory action seems to be suppression nitric oxide (NO) production by activated macrophages resulting from inhibiting NOS (NO synthase)‐2 enzymatic activity (15). Given the substantial resemblance of ocular and follicular IP characteristics (31), it is not unreasonable to estimate that the exact same way of action is being exerted also in the HF.…”

Ocular Immune Privilege and Ocular Melanoma: Parallel Universes or Immunological Plagiarism?

“…TGF-β is produced by Sertoli cells in the testis (Meinhardt and Hedger, 2011), in the hair follicle (Kinori et al, 2011), and by the placenta (Niederkorn, 2006). Moreover, murine embryonic stem cells (ESCs) themselves upregulate TGF-β2 and create an “ ad hoc ” immune privileged niche in the bone marrow (Robertson et al, 2007).…”

“…Moreover, murine embryonic stem cells (ESCs) themselves upregulate TGF-β2 and create an “ ad hoc ” immune privileged niche in the bone marrow (Robertson et al, 2007). The hair follicle, placenta, and Leydig cells of the testis elaborate α-MSH, which also suppresses T cell immunity in situ (Niederkorn, 2006; Kinori et al, 2011; Meinhardt and Hedger, 2011). Although it is not a secreted soluble factor, IDO acts to locally suppress T cell-mediated inflammation by depleting tryptophan and starving T cells.…”

“…Interestingly, the hematopoietic stem cells are lost if the hosts are depleted of CD4 + CD25 + T regs (Fujisaki et al, 2011). To date no studies have examined if the hair follicle environment promotes the induction of immune deviation or the generation of T regs (Kinori et al, 2011). …”

“…Protecting stem cells from immune-mediated elimination has obvious survival benefits for the host and in the case of the placenta, for the survival of the species. It is noteworthy that many of the mechanisms that sustain immune privilege in the central nervous system (i.e., eye and brain) are also employed in sites where stem cells reside (e.g., testis, hair follicle, and placenta) and by stem cells themselves (Arck et al, 1997; Moffett-King, 2002; Aluvihare et al, 2004, 2005; Niederkorn, 2006; Robertson et al, 2007; Fujisaki et al, 2011; Kinori et al, 2011; Meinhardt and Hedger, 2011; Mital et al, 2011). …”