Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata

Britva, Rimma Laufer; Keren, Aviad; Bertolini, Marta; Ullmann, Yehuda; Paus, Ralf; Gilhar, Amos

doi:10.7554/elife.80768

Cited by 6 publications

(3 citation statements)

References 137 publications

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“…They also showed that human AA skin (vs. control skin) is enriched with overall T lymphocytes (23.74% vs. 11.49%), CD8+ T lymphocytes (9.85% vs. 4.11%), regulatory T lymphocytes (2.02% vs. 0.64%), NK T lymphocytes (4.10% vs. 0.85%), and γδ T lymphocytes (2.49% vs. 1.00%), whereas no significant difference is observed in the frequency of CD4+ T lymphocytes between the AA and control skin. Additionally, innate lymphoid cell type 1 (ILC1)-like cells expressing eomesodermin (eomes, required for both ILC1 and NK cell development), CD49a, and NKG2D, may be involved in AA induction via IFN-γ secretion in human [35]. Abnormal interactions between perifollicular mast cells and CD8+ T lymphocytes are also implicated in both mouse and human AA [36].…”

Section: Pathogenesis Of Alopecia Areata (Aa)mentioning

confidence: 99%

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences

Yamaguchi,

Peeva

2024

IJMS

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Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

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Section: Pathogenesis Of Alopecia Areata (Aa)mentioning

confidence: 99%

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences

Yamaguchi,

Peeva

2024

IJMS

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“…Under physiological circumstances, HFs enjoy a status of relative IP, namely in the bulge and anagen hair bulb. The IP status limits the development of autoimmune responses but can be compromised by endogenous and exogenous stressors [71][72][73][74][75][76][77]. Therefore, we asked whether the epilation-induced HF trauma affects the expression of MHC class Ia and/or the "no danger" signal CD200, two key elements of HF IP [54,74,75,78].…”

Section: Epilation Ex Vivo Transiently Perturbs Hf Immune Privilegementioning

confidence: 99%

Mechanical epilation exerts complex biological effects on human hair follicles and perifollicular skin: An ex vivo study approach

Bertolini,

Gherardini,

Chéret

et al. 2023

Intern J of Cosmetic Sci

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ObjectiveElectrical epilation of unwanted hair is a widely used hair removal method, but it is largely unknown how this affects the biology of human hair follicles (HF) and perifollicular skin. Here, we have begun to explore how mechanical epilation changes selected key biological read‐out parameters ex vivo within and around the pilosebaceous unit.MethodsHuman full‐thickness scalp skin samples were epilated ex vivo using an electro‐mechanical device, organ‐cultured for up to 6 days in serum‐free, supplemented medium, and assessed at different time points by quantitative (immuno‐)histomorphometry for selected relevant read‐out parameters in epilated and sham‐epilated control samples.ResultsEpilation removed most of the hair shafts, often together with fragments of the outer and inner root sheath and hair matrix. This was associated with persistent focal thinning of the HF basal membrane, decreased melanin content of the residual HF epithelium, and increased HF keratinocyte apoptosis, including in the bulge, yet without affecting the number of cytokeratin 15+ HF epithelial stem cells. Sebocyte apoptosis in the peripheral zone was increased, albeit without visibly altering sebum production. Epilation transiently perturbed HF immune privilege, and increased the expression of ICAM‐1 in the bulge and bulb mesenchyme, and the number of perifollicular MHC class II+ cells as well as mast cells around the distal epithelium and promoted mast cell degranulation around the suprabulbar and bulbar area. Moreover, compared to controls, several key players of neurogenic skin inflammation, itch, and/or thermosensation (TRPV1, TRPA1, NGF, and NKR1) were differentially expressed in post‐epilation skin.ConclusionThese data generated in denervated, organ‐cultured human scalp skin demonstrate that epilation‐induced mechanical HF trauma elicits surprisingly complex biological responses. These may contribute to the delayed re‐growth of thinner and lighter hair shafts post‐epilation and temporary post‐epilation discomfort. Our findings also provide pointers regarding the development of topically applicable agents that minimize undesirable sequelae of epilation.

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“…To address this complication, skin lesions could be induced in healthy skin. IL-2-activated peripheral blood mononuclear cells injection causes symptoms of alopecia areata [ 47 , 58 , 77 ].…”

Section: Basic Principles In Xenotransplantationmentioning

confidence: 99%

Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation

Cherkashina,

Morgun,

Rippa

et al. 2023

IJMS

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Most of the knowledge about human skin homeostasis, development, wound healing, and diseases has been accumulated from human skin biopsy analysis by transferring from animal models and using different culture systems. Human-to-mouse xenografting is one of the fundamental approaches that allows the skin to be studied in vivo and evaluate the ongoing physiological processes in real time. Humanized animals permit the actual techniques for tracing cell fate, clonal analysis, genetic modifications, and drug discovery that could never be employed in humans. This review recapitulates the novel facts about mouse skin self-renewing, regeneration, and pathology, raises issues regarding the gaps in our understanding of the same options in human skin, and postulates the challenges for human skin xenografting.

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Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata

Cited by 6 publications

References 137 publications

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences

Mechanical epilation exerts complex biological effects on human hair follicles and perifollicular skin: An ex vivo study approach

Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation

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