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Int J Trichology. 2015 Jan-Mar;7(1):16-23. doi: 10.4103/0974-7753.153451.

Hair Follicle Plasticity with Complemented Immune-modulation Following Follicular Unit Extraction.

Azar RP1, Thomas AH2, Lindner G2.

Author information

Abstract

BACKGROUND:

During hair transplantation as an effective therapy for androgenetic alopecia, hair follicles were typically trans-located from the nonaffected occipital to the balding frontal or vertex region of the scalp. Although this is an autologous intervention, the donor and recipient hair follicle tissue differ in composition and local environment.

SETTINGS AND DESIGN:

In two case studies, we investigated the changes in hair follicle morphology and the immune status of scalp and body hair follicles from different origins transplanted to the eyebrows and the frontal scalp using follicular unit extraction.

RESULTS:

Quantitative histomorphometry and immunohistochemistry revealed a transformation in hair follicle length and dermal papilla size of the scalp, chest and beard hair follicles, which had been re-extracted after a 6-month period posttransplantation. Furthermore, a significant infiltration of B and T lymphocytes as well as macrophages could be observed most prominently in the infundibulum of transplanted hair follicles.

CONCLUSION:

The presented results demonstrate that hair follicle units from different body sites are capable to replace miniaturized or degraded hair follicles in different recipient areas like scalp or eyebrows as they keep their intrinsic capability or acquire the potential to readjust plastically within the beneficiary skin region. The essential secretory crosstalk underlying the observed tissue remodeling is possibly mediated by the infiltrating immune cells.

KEYWORDS:

Dermal papilla; hair follicle plasticity; hair transplantation; intermittent follicular unit extraction

J Agric Food Chem. 2014 Dec 10;62(49):11854-61. doi: 10.1021/jf503184s. Epub 2014 Nov 26.

Stimulatory effect of Brazilian propolis on hair growth through proliferation of keratinocytes in mice.

Miyata S1, Oda Y, Matsuo C, Kumura H, Kobayashi K.

Author information

Abstract

Propolis is a natural honeybee hive product with the potential for use in the treatment of dermatological conditions, such as cutaneous abrasions, burns, and acne. In this study, we investigated whether propolis stimulates hair growth in mice. Ethanol-extracted propolis, which contains various physiologically active substances such as caffeic acid and kaempferol, stimulated anagen induction in shaved back skin. Anagen induction occurred without any detectable abnormalities in the shape of the hair follicles (HFs), hair stem cells in the bulge, proliferating hair matrix keratinocytes in thehair bulb, or localization of versican in the dermal papilla. Propolis treatment also stimulated migration of hair matrix keratinocytes into the hair shaft in HFs during late anagen in the depilated back skin. Organotypic culture of skin containing anagen stage HFs revealed significant stimulation of hairmatrix keratinocyte proliferation by propolis. Furthermore, propolis facilitated the proliferation of epidermal keratinocytes. These results indicate that propolis stimulates hair growth by inducing hair keratinocyte proliferation.

KEYWORDS:

anagen induction; epidermis; hair growth; keratinocyte; propolis

Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10648-53. doi: 10.1073/pnas.1402862111. Epub 2014 Jul 2.

FGF5 is a crucial regulator of hair length in humans.

Higgins CA1, Petukhova L2, Harel S1, Ho YY1, Drill E1, Shapiro L3, Wajid M4, Christiano AM5.

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Abstract

Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5. We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.

KEYWORDS:

catagen; consanguineous families; hair cycling; next-generation sequencing

Biomed Res Int. 2015;2015:730139. doi: 10.1155/2015/730139. Epub 2015 Jan 1.

Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice.

Lin WH1, Xiang LJ2, Shi HX2, Zhang J2, Jiang LP3, Cai PT2, Lin ZL4, Lin BB2, Huang Y2, Zhang HL4, Fu XB5, Guo DJ6, Li XK2, Wang XJ2, Xiao J2.

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Abstract

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growthpromoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.

PMID:

 

25685806

 

[PubMed - in process] 

PMCID:

 

PMC4313060

 

Free PMC Article

Exp Dermatol. 2012 Oct;21(10):796-8. doi: 10.1111/j.1600-0625.2012.01572.x. Epub 2012 Aug 22.

The effect of sebocytes cultured from nevus sebaceus on hair growth.

Lee WJ, Cha HW, Lim HJ, Lee SJ, Kim do W.

Abstract

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT-PCR, western blot assay and immunofluorescence staining. NSS- and NS-conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS-conditioned medium-treated group, compared with the control and NS-conditioned medium-treated groups. An increase in expression of fibroblast growth factor (FGF)-5, Dickkopf-1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth-suppressing bioactive factors, including FGF-5, and a decrease in expression of hair growth-stimulating factors.

© 2012 John Wiley & Sons A/S.

J Clin Endocrinol Metab. 2014 Apr;99(4):1393-9. doi: 10.1210/jc.2013-2607. Epub 2014 Jan 16.

Estrone sulfate source of estrone and estradiol formation in isolated human hair roots: identification of a pathway linked to hair growth phase and subject to site-, gender-, and age-related modulations.

Wehner G1, Schweikert HU.

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Abstract

BACKGROUND:

The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender, and age.

METHODS:

Healthy male (n = 18) and female (n = 20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites.

RESULTS:

Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects <50 years old, estrogen synthesis in scalp hair was lower in men than in women. Comparable levels of estrogen formation were observed in 1) male and female axillary and pubic hair and 2) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men <50 years old. With increasing age, estrogen synthesis increased in men and decreased in women. In telogen hair from all body sites, the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86% in men and women, respectively.

CONCLUSIONS:

Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.

PMID:

 

24432990

 

[PubMed - indexed for MEDLINE]

Biol Rev Camb Philos Soc. 2014 Nov 19. doi: 10.1111/brv.12151. [Epub ahead of print]

Resting no more: re-defining telogen, the maintenance stage of the hair growth cycle.

Geyfman M1, Plikus MV, Treffeisen E, Andersen B, Paus R.

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Abstract

The hair follicle (HF) represents a prototypic ectodermal-mesodermal interaction system in which central questions of modern biology can be studied. A unique feature of these stem-cell-rich mini-organs is that they undergo life-long, cyclic transformations between stages of active regeneration (anagen), apoptotic involution (catagen), and relative proliferative quiescence (telogen). Due to the low proliferation rate and small size of the HF during telogen, this stage was conventionally thought of as a stage of dormancy. However, multiple lines of newly emerging evidence show that HFs during telogen are anything but dormant. Here, we emphasize that telogen is a highly energy-efficient default state of the mammalian coat, whose function centres around maintenance of the hair fibre and prompt responses to its loss. While actively retaining hair fibres with minimal energy expenditure, telogen HFs can launch a new regeneration cycle in response to a variety of stimuli originating in their autonomous micro-environment (including its stem cell niche) as well as in their external tissue macro-environment. Regenerative responses of telogen HFs change as a function of time and can be divided into two sub-stages: early 'refractory' and late 'competent' telogen. These changing activities are reflected in hundreds of dynamically regulated genes in telogen skin, possibly aimed at establishing a fast response-signalling environment to trauma and other disturbances of skin homeostasis. Furthermore, telogen is an interpreter of circadian output in the timing of anagen initiation and the key stage during which the subsequent organ regeneration (anagen) is actively prepared by suppressing molecular brakes on hair growth while activating pro-regenerative signals. Thus, telogen may serve as an excellent model system for dissecting signalling and cellular interactions that precede the active 'regenerative mode' of tissue remodeling. This revised understanding of telogen biology also points to intriguing new therapeutic avenues in the management of common human hair growth disorders.

© 2014 Cambridge Philosophical Society.

KEYWORDS:

energy; gene expression; hair growth cycle; hair regeneration; telogen

Arch Dermatol Res. 2015 Mar;307(2):171-81. doi: 10.1007/s00403-014-1521-3. Epub 2014 Dec 14.

Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice.

Wang L1, Guo LL, Wang LH, Zhang GX, Shang J, Murao K, Chen DF, Fan XH, Fu WQ.

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Abstract

Neuropeptide substance P (SP) and reactive oxygen species (ROS) have been demonstrated to play an important role in psychological stress-induced alteration of hair cycle, the underlying mechanism remains unknown. The present study aims to investigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronic psychological stress model) induced abnormal of hair cycle and induction of autophagy. Mouse CRS model was applied for 18 days with or without treatment antioxidant Tempol (a free radical scavenger) or SP receptor (NK1) antagonist (RP67580). After CRS procedure, hair growth cycle, oxidative stress markers and skin tissue autophagy levels were analyzed by ELISA or western blot. Our results revealed that CRS reduced body weight gain, distance of movement and times of standing, affected hair cycle by prolonging the telogen stage and delaying subsequent anagen and catagen stage. In addition, CRS resulted in increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase of autophagy markers (microtubule-associated proteins, light chain 3-II, LC3-II, and Beclin-1) in mice skin. Treatment with Tempol restored GSH-Px activity, and significantly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, as well as normalized hair cycle. In addition; RP67580 also restored SOD and GSH-Px activities, and markedly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, and normalized hair cycle. Our study provides the first strong evidence for SP and ROS play a role not only in alteration of hair cycle but also in induction of autophagy in psychological stress model, suggesting autophagy may contribute to psychological stress-induced abnormal of hair cyc

J Dermatol. 2014 Aug;41(8):716-23. doi: 10.1111/1346-8138.12570.

Prevention of hair graying by factors that promote the growth and differentiation of melanocytes.

Endou M1, Aoki H, Kobayashi T, Kunisada T.

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Abstract

Epidermal melanocyte precursors migrate into developing hair follicles to form the melanocyte stem cell system required to supply pigmented melanocytes necessary for hair pigmentation in repetitive hair cycles. Hair graying is caused by irreversible defects in the self-renewal and/or development of follicular melanocyte stem cells in the hair follicles. To investigate the mechanism(s) of hair graying during the normal aging process, we established a hair graying model in mice by repeatedly plucking or shaving trunk hairs. We repeatedly plucked or shaved trunk hairs to induce and accelerate the hair graying and counted the gray hairs. By using this functional model of hair graying in mice, we assessed the effects of genes known to affect melanocyte development, such as Kitl, hepatocyte growth factor (HGF) and endotheline 3 (ET3). After increasing the total numbers of cumulative hair cycles by plucking or shaving, we observed a significant increase in the gray hair of C57BL/6 mice. Kitl expression in the skin was the most effective for preventing hair graying and a significant effect was also confirmed for HGF and ET3 expression. The repeated hair plucking or shaving led to hair graying without any genetic lesion. Kitl is a more effective factor for prevention of hair graying than HGF or ET3. Our simple model of hair graying may provide a basic tool for screening the molecules or reagents preventing the progression of hair graying.

© 2014 Japanese Dermatological Association.

J Biomol Screen. 2013 Apr;18(4):462-73. doi: 10.1177/1087057112464574. Epub 2012 Nov 27.

Visible-to-near IR quantum dot-based hypermulticolor high-content screening of herbal medicines for the efficacy monitoring of hair growth promotion and hair loss inhibition.

Kim MJ1, Lim C, Lee JY, Im KR, Yoon KS, Song JM.

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Abstract

There is a growing interest in alopecia prevention strategies, as the number of alopecia patients is increasing. We examine the efficacy of herbal medicine for hair growth promotion/hair loss inhibition in two cell lines via Western blot and high-content screening (HCS). Nine herbal extracts were obtained from three different herbal medicine mixtures using 3 different extraction methods. Five target proteins-IGF-1 (insulin-like growth factor-1), TGF-β2 (transforming growth factor-β2), VEGF (vascular endothelial growth factor), DKK-1 (Dickkopf-1), and Wnt5α-were observed for the assessment of hair growth promotion/hair loss inhibition efficacy. The efficacies of nine extracts were compared with minoxidil as control. Efficacy was defined as a rise in the expression levels of IGF-1, VEGF, and Wnt5α but a decrease in DKK-1 and TGF-β2. Intracellular concurrent imaging of these proteins was successfully achieved using HCS, employing visible-to-near infrared probing based on quantum-antibody conjugates and hypermulticolor imaging.

PMID:

 

23190736

 

[PubMed - indexed for MEDLINE]

Appl Microbiol Biotechnol. 2014 Jan;98(2):695-704. doi: 10.1007/s00253-013-4929-3. Epub 2013 Apr 30.

High-efficiency production of bioactive recombinant human fibroblast growth factor 18 in Escherichia coli and its effects on hair follicle growth.

Song L1, Huang Z, Chen Y, Li H, Jiang C, Li X.

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Abstract

Using fusion tags, expression of recombinant human fibroblast growth factor 18 (rhFGF18) in mammalian cells and Escherichia coli has been extensively used for fundamental research and clinical applications, including chondrogenesis and osteogenesis, hair growth, and neuroprotection. However, high-level rhFGF18 expression is difficult and the products are often not homogeneous. Furthermore, fusion-tagged protein has higher immunogenicity and lower bioactivity, and the removal of the fused tag is expensive. To overcome the limitations of fusion-tagged expression of protein and to prepare soluble highly bioactive rhFGF18, we have developed a rapid and efficient expression strategy. Optimized hFGF18 gene was amplified by polymerase chain reaction and cloned into pET22b and pET3c vectors, then transformed into E. coli strains Origima (DE3) and BL21 (DE3)PlysS. The best combination of plasmid and host strain was selected, and only Origima (DE3)/pET3c-rhFGF18 was screened for high-level expressed rhFGF18. Under optimal conditions in a 30-L fermentor, the average bacterial yield and expression level of rhFGF18 of three batches were more than 652 g and 30 % respectively, after treatment with 1 mM isopropyl-thio-β-galactopyranoside for 10 h at 25 °C. The target protein was purified by CM Sepharose FF and heparin affinity chromatography. The purity of rhFGF18 was shown by HPLC to be higher than 95 %, and the yield was 155 mg/L. In vitro MTT assays demonstrated that the purified rhFGF18 could stimulate significant proliferation of NIH3T3 cells, and animal experiments showed that rhFGF18 could effectively regulate hair growth. In conclusion, this may be a better method of producing rhFGF18 to meet the increasing demand in its pharmacological application.

PMID:

 

23624709

 

[PubMed - indexed for MEDLINE]

Exp Dermatol. 2014 Dec;23(12):865-7. doi: 10.1111/exd.12504.

Parathyroid hormone-related peptide and the hair cycle - is it the agonists or the antagonists that cause hairgrowth?

Gensure RC1.

Author information

Abstract

While the effects of PTHrP have been studied for almost 20 years, most of these studies have focused on effects on the termination of the anagen phase, giving an incomplete picture of the overall effect of PTHrP on the hair cycle. PTHrP was determined in several experimental models to promote transition of hair follicles from anagen to catagen phase, which by itself would suggest that PTHrP blockade might prolong the anagen phase and promote hair growth. However, clinical trials with topically applied PTHrP antagonists have been disappointing, leading to a reconsideration of this model. Additional studies performed in mouse models where hair follicles are damaged (alopecia areata, chemotherapy-induced alopecia) suggest that PTHrP has effects early in the hair cycle as well, promoting hair follicles' entry into anagen phase and initiates the hair cycle. While the mechanism of this has yet to be elucidated, it may involve activation of the Wnt pathway. Thus, the overall effect of PTHrP is to stimulate and accelerate the hair cycle, and in the more clinically relevant models of hair loss where hair follicles have been damaged or become quiescent, it is the agonists, not the antagonists, which would be expected to promote hair growth.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Eur J Dermatol. 2014 Sep-Oct;24(5):568-76. doi: 10.1684/ejd.2014.2428.

Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL).

Van Neste D1.

Author information

Abstract

BACKGROUND:

The words "hair growth" frequently encompass many aspects other than just growth.

OBJECTIVES:

Report on a validation method for precise non-invasive measurement of thickness together with linear hair growth rates of individual hairfibres. To verify the possible correlation between thickness and linear growth rate of scalp hair in male pattern hair loss as compared with healthy male controls.

MATERIALS AND METHODS:

To document the process of validation of hair growth measurement from in vivo image capturing and manual processing, followed by computer assisted image analysis. We analysed 179 paired images obtained with the contrast-enhanced-phototrichogram method with exogen collection (CE-PTG-EC) in 13 healthy male controls and in 87 men with male pattern hair loss (MPHL).

RESULTS:

There was a global positive correlation between thickness and growth rate (ANOVA; p<0.0001) and a statistically significantly (ANOVA; p<0.0005) slower growth rate in MPHL as compared with equally thick hairs from controls. Finally, the growth rate recorded in the more severe patterns was significantly (ANOVA; P ≤ 0.001) reduced compared with equally thick hair from less severely affected MPHL or controls subjects.

CONCLUSION:

Reduced growth rate, together with thinning and shortening of the anagen phase duration in MPHL might contribute together to the global impression of decreased hair volume on the top of the head. Amongst other structural and functional parameters characterizing hair follicle regression, linear hair growth rate warrants further investigation, as it may be relevant in terms of self-perception of hair coverage, quantitative diagnosis and prognostic factor of the therapeutic response.

KEYWORDS:

androgenetic alopecia; clinical trial; imaging; male pattern hair loss; phototrichogram; scalp hair

Int J Cosmet Sci. 2014 Dec;36(6):531-6. doi: 10.1111/ics.12151. Epub 2014 Sep 3.

Changes in Chinese hair growth along a full year.

Liu C1, Yang J, Qu L, Gu M, Liu Y, Gao J, Collaudin C, Loussouarn G.

Author information

Abstract

OBJECTIVE:

To confirm the existence of seasonal hair growth cycle among Chinese subjects and objectivize the seasonal effect of hair loss; the hairgrowth parameters of Chinese volunteers were followed monthly for an entire year on the same area of vertex.

METHODS:

The hair growth parameters of 41 Chinese volunteers (women and men), free from alopecia, were recorded monthly along an entire year using the phototrichogram technique.

RESULTS:

Results show an increased rate of telogen hairs (growing arrest) around August-September in the study group, as previously reported in European subjects albeit of a lower extent and remaining within the normal range of healthy head hair parameters. The possible effects of latitude and daylight duration are discussed.

CONCLUSION:

Data confirm that Chinese hairs present characteristics of the most developed and fast growing terminal fibres, as compared to other non-Asian ethnics.

© 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

KEYWORDS:

hair growth; hair treatment; phototrichogramme; skin physiology

J Cosmet Dermatol. 2010 Dec;9(4):267-75. doi: 10.1111/j.1473-2165.2010.00520.x.

Evaluation of apoptosis regulatory markers in androgenetic alopecia.

El-Domyati M1, Attia S, Saleh F, Bassyouni M, Barakat M, Abdel-Wahab H.

Author information

Abstract

BACKGROUND:

Androgenetic alopecia (AGA) is a common androgen-induced progressive disorder; the pathways of which are regulated by local genetic codes and hormonal control. Meanwhile, it is unclear whether an altered proliferation or increased apoptosis could contribute to its pathogenesis.

AIMS:

To evaluate the role of some apoptosis regulatory markers and follicular proliferation in the pathogenesis of AGA.

PATIENTS/METHODS:

Thirty biopsies were taken from the frontal (bald) area and occipital (hair-bearing) area of 15 male patients with AGA, as well as five specimens from the frontal area of five age-matched controls. The biopsies were stained with apoptosis regulatory markers (Bcl-2, p53, Bax & Fas) and PCNA (proliferating cell nuclear antigen), as well as TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling) staining for the detection of DNA fragmentation in apoptotic cells.

RESULTS:

Bcl-2 expression was localized to epidermal basal layer and follicular dermal papilla with highly significant correlation with PCNA expression (P < 0.001). Perifollicular lymphocytic infiltrate of the bald area showed significant expression of Bcl-2. However, pro-apoptotic Bax and Fas were expressed in the epidermis and not in the hair follicles which does not show any apoptotic keratinocytes by TUNEL staining.

CONCLUSION:

The low proliferation rate in the bald area of patients, together with persistent perifollicular inflammatory infiltrate as evidenced by the anti-apoptotic Bcl-2 expression in dermal lymphocytes, would result in follicular miniaturization and fibrosis.

© 2010 Wiley Periodicals, Inc.