毛囊免疫赦免与斑秃

近年来研究证实生长期毛囊为免疫赦免部位 ,生长期毛球主要组织相容性复合体Ⅰ分子表达呈阴性。斑秃主要累及生长期毛囊 ,以毛囊周围淋巴细胞浸润和毛囊上皮细胞异常表达主要组织相容性复合体Ⅰ和Ⅱ分子为特征。因此 ,目前认为斑秃发病与生长期毛囊丧失免疫赦免地位有关     

毛囊免疫赦免机制研究进展

生长期毛囊具有的免疫赦免特征是保护毛囊及毛干细胞免受免疫攻击和毁损,维持毛发正常生长的重要机制。该环境的破坏则会导致包括斑秃在内的多种毛发疾病。研究表明,赦免环境的建立和维护与MHC限制性抗原递呈途径、Fas-FasL系统及局部免疫抑制性细胞因子环境等有关。     

斑秃毛囊免疫赦免机制的进展

近年来大量研究显示,生长期毛囊也是免疫赦免器官之一。有学者提出,斑秃毛囊免疫赦免消失导致斑秃发生。其中一些炎症因子在免疫赦免丧失及重建过程中起到关键作用。而黑素细胞相关肽在发病机制中可能就是自身抗原。     

毛囊免疫赦免与斑秃

近年来研究证实生长期毛囊为免疫赦免部位，生长期毛球主要组织相容性复合体I 分子表达呈阴性。斑秃主要累及生长期毛囊，以毛囊周围淋巴细胞浸润和毛囊上皮细胞异常表达主要组织相容性复合体I和Ⅱ分子为特征。因此，目前认为斑秃发病与生长期毛囊丧失免疫赦免地位有关。     

毛囊免疫赦免与相关皮肤病的研究进展

免疫赦免的丢失是原发性瘢痕性脱发和斑秃的主要机制之一,免疫赦免指特定的组织和解剖结构,通过获得免疫效应细胞在外来抗原入侵时保护自己免受免疫攻击.因为具备独特的免疫和激素环境,生长期毛囊的毛球和毛囊外根鞘的隆突区被认为具备“相对免疫赦免”的能力.局部免疫赦免的丢失导致毛囊自身抗原的免疫反应,可以引起斑秃、原发性瘢痕性脱发等疾病发生.恢复免疫赦免有助于治疗这些疾病.     

人类毛囊黑素细胞的研究现况

毛囊黑素细胞在形态分布，抗原表达及功能作用上与表皮黑素细胞不同；其生物学特性受角朊 细胞，激素和紫外线等机体内，外多种因素的调控。     

斑秃毛囊退行性变及局部炎症细胞浸润的研究进展

斑秃是一种非瘢痕性的炎症性脱发性疾病,病情多能自限,但容易复发。斑秃发病机制不明,组织病理上表现为生长期毛囊周围炎症浸润及毛囊退行性变两个部分。目前研究认为,内外源因素作用于遗传易感人群引起生长期毛囊深层周围炎症细胞浸润,浸润的炎症细胞及细胞因子、神经肽等形成恶性循环,循环结局为毛囊上皮细胞凋亡,大批毛囊同时陕速进入退行期,导致斑秃发生。     

人类毛囊黑素细胞的研究现况

毛囊黑素细胞在形态分布、抗原表达及功能作用上与表皮黑素细胞不同;其生物学特性受角朊细胞、激素和紫外线等机体内、外多种因素的调控。白癜风皮损中表皮黑素细胞缺失,而毛囊黑素细胞成为其色素恢复的再生来源;相反,斑秃时毛囊黑素细胞受累,而表皮黑素细胞不受影响。研究影响毛囊黑素细胞生存和病变的因素及其机制将对了解白癜风和斑秃的病因、发病机理和开发新的治疗方法具有重要意义。     

细胞因子与斑秃

该文综述了胰岛素样生长因子、表皮生长因子、转化生长因子、肝细胞生长因子等生长因子及双介素１和α肿瘤坏死因子等细胞因子对毛囊生长的调控和上述因子在斑秃毛囊中的变化和作用，人类白细胞抗原和细胞间粘附分子的表达与斑秃的免疫效应有关，毛乳头凋亡不受ｂｃｌ－２原癌基因保护。最后简介了斑秃基因治疗的前景。     

The hair follicle and immune privilege

This essay reviews the available evidence that the proximal hair follicle epithelium generates and maintains an area of relative immune privilege during a defined segment of the hair cycle (i.e., during anagen). This immune privilege is chiefly characterized by a very low level of expression of MHC class Ia antigens and by the local production of potent immunosuppressive agents, such as alpha-MSH and TGF-beta1. We discuss the putative functions of immune privilige of the anagen hair bulb, favoring the view that immune privilege serves mainly to sequester anagen- and/or melanogenesis-associated autoantigens from immune recognition by autoreactive CD8+ T cells. On this basis, we develop how the "immune privilege collapse model" of alopecia areata pathogenesis was conceived. In our discussion of the clinical implications of immune privilege, we outline the currently available evidence in support of this still hypothetical scenario to explain the initiation, progression, and termination of alopecia areata lesions. We review the most recent evidence from our laboratory that alpha-MSH, IGF-1, and TGF-beta1 can downregulate IFN-gamma-induced ectopic MHC class I expression in human anagen hair bulbs in vitro. Finally, we suggest that hair follicle-derived alpha-MSH, IGF-gamma, and TGF-beta1 form part of a constitutively active "IP restoration machinery" of the anagen hair bulb, which we propose to be recruited whenever the hair follicle suffers immune injury. Finally, we sketch some particularly promising avenues for future investigation into the far too long ignored hair follicle immune privilege.     

Immune privilege in hair growth.

Immunostaining techniques were used to investigate the relationship between immune cells, proteoglycan, and class I MHC distribution in skin during the hair cycle in rats. The growth stage, anagen, was characterized by absence of class I MHC staining on most cells of the lower follicle and presence of chondroitin proteoglycan in the follicle sheath and dermal papilla. Immune cells were few in number and not associated with follicles. Dramatic changes were observed during regression in catagen; class I MHC was expressed on all follicle epithelium, large numbers of activated macrophages aggregated around the follicles, and the chondroitin proteoglycans disappeared from the follicle sheath and dermal papilla. During the resting stage, telogen, class I MHC remained on cells of the secondary germ, but macrophages and chondroitin proteoglycans were absent. These observations lead us to propose a hypothesis of immune privilege in hair growth.     

Mechanisms of immune privilege in the eye and hair follicle

It has been recognized for over a century that the eye is endowed with remarkable properties that permit the long-term survival of foreign tumor and tissue grafts that are normally rejected at extraocular sites. This ocular immune privilege was originally attributed to a putative sequestration of antigens in the eye as a result of the conspicuous absence of intraocular lymphatic drainage channels. In the last 30 years, a sizeable body of information indicates that ocular immune privilege is a product of multiple anatomical, physiological, and immunoregulatory processes. Ocular tissues and fluids express a wide variety of anti-inflammatory and immunosuppressive molecules, including CD95L (FasL), transforming growth factor-beta, macrophage migration inhibitory factor, alpha-melanocyte-stimulating hormone, calcitonin gene-related peptide, somatostatin, and complement regulatory proteins. Moreover, antigens entering the anterior chamber of the eye evoke a unique form of immune deviation that culminates in the antigen-specific suppression of TH1 immune responses. Finally, the intraocular milieu contains both cell membrane and soluble factors that inhibit both the adaptive and innate immune systems. The hair follicle is also recognized for its immune privilege. Like the anterior chamber of the eye, it produces anti-inflammatory and immunosuppressive cytokines, such as transforming growth factor-beta and adrenocorticotrophic hormone. The cells of the hair follicle display limited expression of class Ia MHC molecules and, like cells that line the anterior chamber of the eye, are protected against CD8+ cytotoxic T lymphocyte attack. Gaining a better understanding of the immune privilege of the hair follicle may provide insights into the regulation and pathogenesis of immune-mediated diseases of the skin.     

The human hair follicle immune system: cellular composition and immune privilege

The immunology of the hair follicle, its relationship with the 'skin immune system' and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and gammadelta T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA-A, -B, -C) and beta2-microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.     

Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack

Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56(+)/NKG2D(+) NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56(+)/NKG2D(+) NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56(+) NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.     

Enzymology of the hair follicle

Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. A genetic predisposition is a feature of AGA, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far move advanced, and human hair follicles are not only targets for androgens, but also reveal an active androgen metabolism, with the ability to convert several androgens by different steroidogenic enzymes. Recent results suggest that the dermal papilla of the hair follicle expresses abundant type 2 5a-reductase, 3b-HSD and steroid sulfatase activity. Therefore, current information about the androgen metabolism in hair follicles is reviewed and the potential impact on future therapeutic approaches is discussed.     

Estrogens and the hair follicle

While it is undisputed that estrogens (17β‐estradiol, E2) are mainly involved in skin physiology and operate as potent hair growth modulators, our knowledge about the estrogen target cells in skin and exact signaling pathways is still very limited. The current review provides an overview of estrogen effects on hair follicle cycling, cutaneous expression of estrogen receptors, and potential functions of estrogens in hair biology. We discuss potential target genes of estrogen receptor‐mediated signaling in the skin, explore the interplay of estrogens with other hormones, growth factors and enzymes, and define major open questions in this intriguing and far too long neglected area of hair research.     

Apoptosis in the hair follicle

Apoptosis plays an important role in many physiological processes, ranging from morphogenetic events to adult tissue homeostasis, and defects in its regulation contribute to many disorders. Here we review molecular mechanisms of apoptosis in the hair follicle (HF), whose cyclical growth pattern is repeatedly interrupted by apoptosis-driven involution (catagen). We review the common mechanisms underlying apoptosis in the HF during catagen, as well as differences in the regulation of apoptosis between distinct HF cell populations. An overview is provided on the expression and function of molecules involved in the control of various phases of the apoptotic process during catagen.     

Integral hair lipid in human hair follicle

Integral hair lipid (IHL) is bound to the keratinized cell surface to make an environmentally resistant lipid envelope. It is mainly positioned on the hair cuticle and inner root sheath. IHL in the hair follicle may regard as hair barrier to be similar to the epidermal lipid layer functioning as skin barrier. Major constituents of IHL are fatty acid, phytosphingosine, ceramide in decreasing order. Minor constituents of IHL are cholesterol, cholesterol sulfate and cholesterol oleate. Cuticle or cortical cell surface in hair are abundant in fatty acids unlike the keratinized area of epidermis or sebaceous gland, and about 30-40% of such fatty acids are composed of 18-methyl-eicosanoic acid which is known to be bound to proteins by ester or thioester bond. Various factors including moisture, solvent, oxidative damage during bleaching or permanent waving affect IHL. Photochemical changes also can occur in IHL as well as in hair protein and hair pigment. Lipid metabolism is thought to play an essential role in lipid envelope of hair, but also involvement in hair development and function.