Developmentally programmed early-age skin localization of iNKT cells supports local tissue development and homeostasis

Wang, Wei-Bei; Lin, Yang-Ding; Zhao, Lei; Liao, Chang; Zhang, Yang; Davila, Micha L.; Sun, Jasmine; Chen, Yidong; Xiong, Na

doi:10.1038/s41590-022-01399-5

Cited by 8 publications

(2 citation statements)

References 53 publications

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“…Studies have also shown the functional significance of iNKT cells not only for protection against pathogens but also in the establishment and maintenance of tissue homeostasis ( Figure 1 ). Tissue accumulation of iNKT cells during fetal life is necessary to maintain intestinal tract and skin homeostasis ( 63 , 64 ), and iNKT cells are also involved in regulating peripheral serotonin release. These show that iNKT cells contribute not only to the immune system but also to systemic homeostasis ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Glycolipid antigen recognition by invariant natural killer T cells and its role in homeostasis and antimicrobial responses

Hayashizaki,

Kamii,

Kinjo

2024

Front. Immunol.

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Due to the COVID-19 pandemic, the importance of developing effective vaccines has received more attention than ever before. To maximize the effects of vaccines, it is important to select adjuvants that induce strong and rapid innate and acquired immune responses. Invariant natural killer T (iNKT) cells, which constitute a small population among lymphocytes, bypass the innate and acquired immune systems through the rapid production of cytokines after glycolipid recognition; hence, their activation could be used as a vaccine strategy against emerging infectious diseases. Additionally, the diverse functions of iNKT cells, including enhancing antibody production, are becoming more understood in recent years. In this review, we briefly describe the functional subset of iNKT cells and introduce the glycolipid antigens recognized by them. Furthermore, we also introduce novel vaccine development taking advantages of iNKT cell activation against infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Glycolipid antigen recognition by invariant natural killer T cells and its role in homeostasis and antimicrobial responses

Hayashizaki,

Kamii,

Kinjo

2024

Front. Immunol.

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“…To counter tissue destruction during inflammatory insults, hair follicles have evolved an immune privilege (IP) mechanism (3,4). This hair follicle stem cell IP is characterized by low expression of major histocompatibility complex class I (MHC I) for self-tolerance, up-regulation of "no danger" signals such as CD200, generation of an immunosuppressive microenvironment via TGF- secretion, and recruitment of regulatory T cells, Trem2 + macrophages, and invariant natural killer (NK) T cells (5)(6)(7)(8)(9). Autoimmunity mediated by cytotoxic T cells can lead to the destruction of the hair follicle bulb region, which consists of transiently amplifying cells during hair growth, resulting in reversible hair loss known as alopecia areata (AA) in humans (10).…”

Section: Introductionmentioning

confidence: 99%

Scarring hair follicle destruction is driven by the collapse of EGFR-protected JAK-STAT1-sensitive stem cell immune privilege

Strobl,

Klufa,

Jin

et al. 2023

Preprint

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The hair follicle stem cell niche is an immune-privileged microenvironment, characterised by suppressed antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrate the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) from scarring hair follicle degeneration. Mechanistically, disruption of EGFR signalling generates a cell intrinsic hypersensitivity within the JAK-STAT1 pathway, compromising the immune privilege in the context of CD8 T cell and NK cell-mediated inflammation. Genetic depletion of either JAK1/2 or STAT1 or topical therapeutic inhibition of JAK1/2 restores the immune privilege and activates stem cells to resume hair growth in mouse models of epidermal and hair follicle specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and from EGFR-independent cicatricial alopecia patients indicate active STAT1 signalling within the hair follicles. Notably, a case study of folliculitis decalvans, characterised by progressive hair loss, scaling and perifollicular erythema, demonstrates successful treatment with systemic JAK1/2 inhibition. Our findings offer mechanistic insights and present a therapeutic strategy for addressing scarring hair follicle destruction associated with EGFR-inhibitor therapy and cicatricial alopecia.

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Mucosal-Associated Invariant T (MAIT) Cell Differentiation and Function

Ascui,

Kronenberg

2024

Reference Module in Life Sciences

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Developmentally programmed early-age skin localization of iNKT cells supports local tissue development and homeostasis

Cited by 8 publications

References 53 publications

Glycolipid antigen recognition by invariant natural killer T cells and its role in homeostasis and antimicrobial responses

Glycolipid antigen recognition by invariant natural killer T cells and its role in homeostasis and antimicrobial responses

Scarring hair follicle destruction is driven by the collapse of EGFR-protected JAK-STAT1-sensitive stem cell immune privilege

Mucosal-Associated Invariant T (MAIT) Cell Differentiation and Function

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