Alopecia Areata: A Review of Disease Pathogenesis

F. Rajabi; L.A. Drake; M.M. Senna; N. Rezaei


The British Journal of Dermatology. 2018;179(5):1033-1048. 

In This Article

Proposed Mechanisms of Immune Privilege Preservation in Hair Follicles

Several mechanisms are claimed to be responsible for maintaining IP (Figure 1). Firstly, the absence of lymphatic drainage and presence of the extracellular matrix may serve as physical barriers to invading immune cells.[24–26] Any immune cells capable of breaching the physical barriers are then presumably targeted by proapoptotic Fas ligand and programmed cell death 1 ligand 1 (PD-L1).[27–30] Although several studies have failed to demonstrate FasL on major histocompatibility complex (MHC)–I-negative HFs, PD-L1 is found on dermal sheath cup cells and dermal papilla cells.[27,28,31]

Figure 1.

The main mechanisms of immune privilege preservation in normal hair follicles. NK cells express a wide range of receptor complexes. The main activating receptor, NKG2D, binds with MICA and ULBP, and the major inhibitory receptor, KIR, binds with HLA molecules. The KIR receptors allow the NK cells to be self-tolerated towards normal cells. HLA, human leucocyte antigen; IFN, interferon; KIR, killer cell Ig-like receptor; MHC, major histocompatibility complex; MICA, MHC class I chain-related A; MIF, macrophage migration inhibitory factor; MSH, melanocyte-stimulating hormone; NK, natural killer; TGF, transforming growth factor; ULBP, UL16–binding protein.

HF cells also produce factors that suppress MHC expression to protect their sequestered antigens. These IP guardians include[24–26] transforming growth factor (TGF)–β, α–melanocyte-stimulating hormone (MSH), indoleamine–2,3–dioxygenase (IDO), protein red encoded by the IK gene (red/IK), interleukin (IL)–10, calcitonin gene-related peptide, insulin-like growth factor–1 and somatostatin.[24,29,32–35]

The downregulation of MHC-I eventually leads to macrophage inhibition and the resultant suppression of interferon (IFN)–γ production.[33,36] Although the absence of MHC-I helps in maintaining the IP, it also poses a threat by activating natural killer (NK) cells ('missing self' phenomena).