Hair Follicle Melanocytes Initiate Autoimmunity in Alopecia Areata: a Trigger Point

Xie, Bo; Sun, Jiayi; Song, Xiuzu

doi:10.1007/s12016-022-08954-w

Cited by 16 publications

(14 citation statements)

References 134 publications

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“…To date, the specific pathogenesis of AA remains unknown, although it has been mainly recognized to be caused by immune disorders and genetic factors. Research studies have revealed that melanocytes may be the trigger point that leads to the hair follicles being attacked by the immune system through oxidative stress injuries or apoptosis ( 31 ). On the other hand, different immune cells cooperatively contribute to the progression of AA ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 99%

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Yang

Liao

et al. 2023

Front. Immunol.

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BackgroundThe most commonly acknowledged non-scarring alopecia are androgenetic alopecia (AGA) and alopecia areata (AA). Previous studies have revealed various risk factors associated with alopecia. However, the relationship between leukocyte telomere length (LTL) and non-scarring alopecia remains unclear.MethodsA two-sample Mendelian randomization (MR) analysis was performed to evaluate the causality between genetically predicted LTL and the risk of non-scarring alopecia. MR analyses were performed using the inverse variance-weighted (IVW) method and complemented with other MR methods.ResultsThe summary statistics of the genome-wide association studies (GWAS) for AGA and AA were obtained from the FinnGen biobank, which included 119,185 and 211,428 individuals, respectively. A total of 126 single nucleotide polymorphisms (SNPs) with genome-wide significance were selected as the instrumental variables for LTL. The MR analyses suggested a causal relationship between LTL and AGA, and the risk of AGA increased by 3.19 times as the genetically predicted LTL was shortened by one standard deviation in log transformed form under the IVW method (OR = 4.19, 95% CI = 1.20–14.61, p = 0.024). The other MR methods also demonstrated a similar trend of the effect of LTL on AGA. There was no causal relationship between LTL and AA (p > 0.05). Sensitivity analyses further demonstrated that the current results were less likely to be affected by confounders and bias.ConclusionOur results suggested a potential causal relationship between LTL and AGA, and shortened LTL was associated with an increased risk of AGA.

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Section: Discussionmentioning

confidence: 99%

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Yang

Liao

et al. 2023

Front. Immunol.

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“…However, almost all black hair has vanished. This is particularly true for early-stage AA sufferers ( 105 ). AA patients exhibit a significant reduction in melanocytes ( 106 ).…”

Section: Hair Follicle Melanocytesmentioning

confidence: 99%

Novel potential therapeutic targets of alopecia areata

Wan

Xie

et al. 2023

Front. Immunol.

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Alopecia areata (AA) is a non-scarring hair loss disorder caused by autoimmunity. The immune collapse of the hair follicle, where interferon-gamma (IFN-γ) and CD8+ T cells accumulate, is a key factor in AA. However, the exact functional mechanism remains unclear. Therefore, AA treatment has poor efficacy maintenance and high relapse rate after drug withdrawal. Recent studies show that immune-related cells and molecules affect AA. These cells communicate through autocrine and paracrine signals. Various cytokines, chemokines and growth factors mediate this crosstalk. In addition, adipose-derived stem cells (ADSCs), gut microbiota, hair follicle melanocytes, non-coding RNAs and specific regulatory factors have crucial roles in intercellular communication without a clear cause, suggesting potential new targets for AA therapy. This review discusses the latest research on the possible pathogenesis and therapeutic targets of AA.

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“…Subsequently, activated CD8 + T cells persist in attacking melanocytes, leading to further melanocyte apoptosis and establishing a detrimental cycle of continuous destruction. [19,36,37] Immuno uorescence staining of CD8 + T cells was performed in H 2 O 2 -induced vitiligo mice model. As illustrated in Fig.…”

Section: T Cellsmentioning

confidence: 99%

Biomimetic Polydopamine Loaded with Janus Kinase Inhibitor for Synergistic Vitiligo Therapy via Hydrogel Microneedles

Li,

Wang,

Zhou

et al. 2024

Preprint

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Background Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes exposure self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. This process further leads to the destruction of melanocytes, resulting in a lack of melanin granules. Additionally, oxidative stress induces keratinocytes to express and release T cell chemotactic factors, exacerbating vitiligo. The reduction of CD8+ T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy. Results In this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA effectively mitigates apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. Simultaneously, PDA alleviates oxidative stress in keratinocytes, leading to a reduction in the expression of chemotactic factors. JAKi, binding to JAK, significantly diminishes the activation of T cells. We precisely deliver this therapeutic agent to the dermis using microneedle (MN) patches, aiming to enhance therapeutic efficacy compared to traditional drug administration methods. After PDA-JAKi MN treatment, the symptoms of vitiligo in mice are alleviated, and the affected areas regain pigmentation. Enhancements have been noted in the dermal thickness within the treated skin area. Concurrently, a decrease in the abundance of immune cells, particularly the infiltration of CD8+ T cells, have been observed. Moreover, there is a notable reduction in interferon-γ (IFN-γ) levels, along with a substantial decrease in the chemotactic factors C-X-C motif chemokine ligand 10 (CXCL10) and C-X-C motif chemokine ligand 16 (CXCL16). Conclusions In summary, PDA-JAKi MN nanoplatform emerges as a promising therapeutic agent in vitiligo treatment.

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Hair Follicle Melanocytes Initiate Autoimmunity in Alopecia Areata: a Trigger Point

Cited by 16 publications

References 134 publications

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study

Novel potential therapeutic targets of alopecia areata

Biomimetic Polydopamine Loaded with Janus Kinase Inhibitor for Synergistic Vitiligo Therapy via Hydrogel Microneedles

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