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Abstract
The skin serves as the primary interface between our body and the external environment and acts as a barrier against entry of physical agents, chemicals, and microbes. Keratinocytes make up the main cellular constitute of the outermost layer of the skin, contributing to the formation of the epidermis, and they are crucial for maintaining the integrity of this barrier. Beyond serving as a physical barrier component, keratinocytes actively participate in maintaining tissue homeostasis, shaping, amplifying, and regulating immune responses in skin. Keratinocytes act as sentinels, continuously monitoring changes in the environment, and, through microbial sensing, stretch, or other physical stimuli, can initiate a broad range of inflammatory responses via secretion of various cytokines, chemokines, and growth factors. This diverse function of keratinocytes contributes to the highly variable clinical manifestation of skin immune responses. In this Review, we highlight the highly diverse functions of epidermal keratinocytes and their contribution to various immune-mediated skin diseases.
Authors
Yanyun Jiang, Lam C. Tsoi, Allison C. Billi, Nicole L. Ward, Paul W. Harms, Chang Zeng, Emanual Maverakis, J. Michelle Kahlenberg, Johann E. Gudjonsson
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Citations to this article (148)
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Emerging Treatments and the Clinical Trial Landscape for Hidradenitis Suppurativa Part I: Topical and Systemic Medical Therapies.
Fragoso NM, Masson R, Gillenwater TJ, Shi VY, Hsiao JL |
Dermatology and Therapy | 2023 |
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Exposure to the anti-microbial chemical triclosan disrupts keratinocyte function and skin integrity in a model of reconstructed human epidermis.
Baur R, Kashon M, Lukomska E, Weatherly LM, Shane HL, Anderson SE |
Journal of Immunotoxicology | 2023 |
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TIME Is Ticking for Cervical Cancer
Kumar V, Bauer C, Stewart JH IV |
Biology | 2023 |
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Fc Epsilon RI–Neuroimmune Interplay in Pruritus Triggered by Particulate Matter in Atopic Dermatitis Patients
Isaifan D, Crovella S, Soubra L, Al-Nesf M, Steinhoff M |
International journal of molecular sciences | 2023 |
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Repressive Control of Keratinocyte Cytoplasmic Inflammatory Signaling
Carman LE, Samulevich ML, Aneskievich BJ |
International journal of molecular sciences | 2023 |
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Rehmannioside A Inhibits TRAF6/MAPK Pathway and Improves Psoriasis by Interfering with the Interaction of HaCaT Cells with IL-17A
Yuan LL, Cao CY |
Clinical, cosmetic and investigational dermatology | 2023 |
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A history of asthma is associated with susceptibility to hidradenitis suppurativa: a population-based longitudinal study.
Kridin K, Shihade W, Weinstein O, Zoller L, Onn E, Cohen A, Solomon-Cohen E |
Archives of Dermatological Research | 2023 |
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The gasdermins: a pore-forming protein family expressed in the epidermis
Slaufova M, Karakaya T, Di Filippo M, Hennig P, Beer HD |
Frontiers in immunology | 2023 |
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The anti-inflammation and skin-moisturizing effects of Boehmeria tricuspis-mediated biosynthesized gold nanoparticles in human keratinocytes
Tran TH, Wang R, Kim H, Kim YJ |
Frontiers in pharmacology | 2023 |
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“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases
Morizane S, Mukai T, Sunagawa K, Tachibana K, Kawakami Y, Ouchida M |
Frontiers in immunology | 2023 |
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Cis-2-Decenoic Acid and Bupivacaine Delivered from Electrospun Chitosan Membranes Increase Cytokine Production in Dermal and Inflammatory Cell Lines
Harrison Z, Montgomery EC, Bush JR, Gupta N, Bumgardner JD, Fujiwara T, Baker DL, Jennings JA |
Pharmaceutics | 2023 |
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Recent advances in epicutaneous immunotherapy and potential applications in food allergy
Hervé PL, Dioszeghy V, Matthews K, Bee KJ, Campbell DE, Sampson HA |
2023 | |
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The Skin and Inflamm-Aging
Agrawal R, Hu A, Bollag WB |
Biology | 2023 |
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Identification of potential miR‑155 target genes in epidermal immune microenvironment of atopic dermatitis patients and their inflammatory effects on HaCaT cells
Wang X, Chen L, Chen X, Liu C, Qiu W, Guo K |
Experimental and therapeutic medicine | 2023 |
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Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney
Garrett S Dunlap, Allison C. Billi, Xianying Xing, Feiyang Ma, Mitra P. Maz, Lam C Tsoi, Rachael Wasikowski, Jeffrey B Hodgin, Johann Gudjonsson, J. Michelle Kahlenberg, Deepak A Rao |
JCI Insight | 2022 |
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Interferon kappa (IFNk) is critical for normal wound repair and is decreased in diabetic wounds
Sonya J. Wolf, Christopher O. Audu, Amrita Joshi, Aaron D. denDekker, William J Melvin, Frank M Davis, Xianying Xing, Rachael Wasikowski, Lam Tsoi, Steven Kunkel, Johann E. Gudjonsson, Mary X. O'Riordan, J. Michelle Kahlenberg, Katherine A. Gallagher |
JCI Insight | 2022 |
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Genomic Control of Inflammation in Human Keratinocytes and Experimental Atopic Dermatitis
Yan Liu, Jozef Zienkiewicz, Huan Qiao, Katherine Gibson-Corley, Kelli Boyd, Ruth Veach, Jack Hawiger |
Scientific Reports | 2022 |
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Alarmin Cytokines as Central Regulators of Cutaneous Immunity
T Hasegawa, T Oka, S Demehri |
Frontiers in immunology | 2022 |
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A multifunctional composite hydrogel as an intrinsic and extrinsic coregulator for enhanced therapeutic efficacy for psoriasis
J Xu, H Chen, Z Chu, Z Li, B Chen, J Sun, W Lai, Y Ma, Y He, H Qian, F Wang, Y Xu |
Journal of nanobiotechnology | 2022 |
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Neutralizing antibody: a savior in the Covid-19 disease
SL Gupta, RK Jaiswal |
Molecular Biology Reports | 2022 |
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Differential gene expression and network analysis in head and neck squamous cell carcinoma
I Habib, F Anjum, T Mohammad, N Sulaimani, A Shafie, M Almehmadi, D Yadav, S Sohal, I Hassan |
Molecular and Cellular Biochemistry | 2022 |
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Unraveling the Role of Sex Hormones on Keratinocyte Functions in Human Inflammatory Skin Diseases
R Gratton, C Vecchio, L Zupin, S Crovella |
International journal of molecular sciences | 2022 |
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The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2
R Vallion, K Hardonnière, A Bouredji, M Damiens, C Deloménie, M Pallardy, P Ferret, S Kerdine-Römer |
Antioxidants | 2022 |
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Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing
M Nizioł, I Ościłowska, W Baszanowska, J Pałka, R Besio, A Forlino, W Miltyk |
Frontiers in Molecular Biosciences | 2022 |
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Interleukin‐38 promotes skin tumorigenesis in an IL‐1Rrp2‐dependent manner
Zhou H, Zhao Q, Yue C, Yu J, Zheng H, Hu J, Hu Z, Zhang H, Teng X, Liu X, Wei X, Zhou Y, Zeng F, Hao Y, Hu Y, Wang X, Zhang C, Gu L, Wu W, Zhou Y, Cui K, Huang N, Li W, Wang Z, Li J |
EMBO reports | 2022 |
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel psoriasis susceptibility locus that is negatively related to IL36G
Alexander Merleev, Antonio Ji-Xu, Atrin Toussi, Lam C Tsoi, Stephanie T Le, Guillaume Luxardi, Xianying Xing, Rachael Wasikowski, William Liakos, Marie-Charlotte Brüggen, James Elder, Iannis E. Adamopoulos, Yoshihiro Izumiya, Annie Riera-Leal, Qinyuan Li, Nikolay Yu. Kuzminykh, Amanda Kirane, Alina I Marusina, Johann Gudjonsson, Emanual Maverakis |
JCI Insight | 2022 |
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Cutaneous Wound Healing: A Review about Innate Immune Response and Current Therapeutic Applications
Adib Y, Bensussan A, Michel L |
Mediators of Inflammation | 2022 |
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Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics
Kwatra SG, Misery L, Clibborn C, Steinhoff M |
IBMS BoneKEy | 2022 |
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Keratinocytes: An Enigmatic Factor in Atopic Dermatitis
Das P, Mounika P, Yellurkar ML, Prasanna VS, Sarkar S, Velayutham R, Arumugam S |
Cells | 2022 |
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Keratinocyte Response to Infection with Sporothrix schenckii
Paredes-Rojas A, Palma-Ramos A, Castrillón-Rivera LE, Mendoza-Pérez F, Navarro-González MD, Arenas-Guzmán R, Castañeda-Sánchez JI, Luna-Herrera J |
Journal of Fungi | 2022 |
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Non-lesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation
Billi AC, Ma F, Plazyo O, Gharaee-Kermani M, Wasikowski R, Hile GA, Xing X, Yee CM, Rizvi SM, Maz MP, Berthier CC, Wen F, Tsoi LC, Pellegrini M, Modlin RL, Gudjonsson JE, Kahlenberg JM |
Science Translational Medicine | 2022 |
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A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective
El-Serafi AT, El-Serafi I, Steinvall I, Sjöberg F, Elmasry M |
International journal of molecular sciences | 2022 |
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The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling.
Wang J, Cui B, Chen Z, Ding X |
Frontiers in Cell and Developmental Biology | 2022 |
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The relevance of complement in pemphigoid diseases: A critical appraisal
Papara C, Karsten CM, Ujiie H, Schmidt E, Schmidt-Jiménez LF, Baican A, Freire PC, Izumi K, Bieber K, Peipp M, Verschoor A, Ludwig RJ, Köhl J, Zillikens D, Hammers CM |
Frontiers in immunology | 2022 |
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Current concepts of photosensitivity in cutaneous lupus erythematosus.
Klein B, Kunz M |
Frontiers in Medicine | 2022 |
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Modulation of Inflammatory Responses by a Non-Invasive Physical Plasma Jet during Gingival Wound Healing
Eggers B, Stope MB, Marciniak J, Mustea A, Deschner J, Nokhbehsaim M, Kramer FJ |
Cells | 2022 |
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Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies
Xu J, Chen H, Qian H, Wang F, Xu Y |
Journal of nanobiotechnology | 2022 |
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miR‐378a regulates keratinocyte responsiveness to interleukin‐17A in psoriasis
Xia P, Pasquali L, Gao C, Srivastava A, Khera N, Freisenhausen JC, Luo L, Rosén E, van Lierop A, Homey B, Pivarcsi A, Sonkoly E |
The British journal of dermatology | 2022 |
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Macrophage-Mediated Inflammation in Skin Wound Healing
Hassanshahi A, Moradzad M, Ghalamkari S, Fadaei M, Cowin AJ, Hassanshahi M |
Cells | 2022 |
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Unravelling the landscape of skin cancer through single-cell transcriptomics.
Srivastava A, Bencomo T, Das I, Lee CS |
Translational oncology | 2022 |
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Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis.
Al Moussawi K, Chung K, Carroll TM, Osterburg C, Smirnov A, Lotz R, Miller P, Dedeić Z, Zhong S, Oti M, Kouwenhoven EN, Asher R, Goldin R, Tellier M, Murphy S, Zhou H, Dötsch V, Lu X |
Cell Reports | 2022 |
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miR-124-3p Delivered Using Exosomes Attenuates the Keratinocyte Response to IL-17A Stimulation in Psoriasis.
Liu S, Gong J |
Oxidative medicine and cellular longevity | 2022 |
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Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.
Wong LS, Yen YT |
International journal of molecular sciences | 2022 |
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Host Response of Human Epidermis to Methicillin-Resistant Staphylococcus aureus Biofilm Infection and Synthetic Antibiofilm Peptide Treatment
Wu B(, Blimkie TM, Haney EF, Falsafi R, Akhoundsadegh N, Hancock RE |
Cells | 2022 |
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Walnut ointment promotes full-thickness burning wound healing: role of linoleic acid
Zhao D, Xiao J, Qiang L, Deng X, An J, Zhang Q, Zhao F, Ma J, Fang C, Guan G, Wu Y, Xie Y |
2022 | |
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Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle
Kovacs D, Bastonini E, Briganti S, Ottaviani M, D\u2019Arino A, Truglio M, Sciuto L, Zaccarini M, Pacifico A, Cota C, Iacovelli P, Picardo M |
Science Advances | 2022 |
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Woodsmoke Extracts Cross-Link Proteins and Induce Cornified Envelope Formation without Stimulating Keratinocyte Terminal Differentiation
LW Lin, MS Denison, RH Rice |
Toxicological Sciences | 2021 |
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Going, Toll-like receptors in skin inflammation and inflammatory diseases
Vijay Kumar |
EXCLI J | 2021 |
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Macrophage-mediated inflammation in diabetic wound repair
S Wolf, W Melvin, K Gallagher |
Seminars in Cell & Developmental Biology | 2021 |
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Interferon Kappa Is a Rheostat for Development of Psoriasiform Inflammation
M Gharaee-Kermani, SN Estadt, LC Tsoi, SJ Wolf, J Liu, X Xing, J Theros, TJ Reed, L Lowe, D Gruszka, NL Ward, JE Gudjonsson, JM Kahlenberg |
Journal of Investigative Dermatology | 2021 |
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Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
NA Evtushenko, AK Beilin, AV Kosykh, EA Vorotelyak, NG Gurskaya |
International journal of molecular sciences | 2021 |
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Wound Healing Effect of Gintonin Involves Lysophosphatidic Acid Receptor/Vascular Endothelial Growth Factor Signaling Pathway in Keratinocytes
SH Choi, KJ Won, R Lee, HS Cho, SH Hwang, SY Nah |
International journal of molecular sciences | 2021 |
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Insights into the Pathogenesis of HS and Therapeutical Approaches
E Rosi, MT Fastame, I Scandagli, AD Cesare, F Ricceri, N Pimpinelli, F Prignano |
Biomedicines | 2021 |
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The Modulatory Influence of Plant-Derived Compounds on Human Keratinocyte Function
A Merecz-Sadowska, P Sitarek, K Zajdel, E Kucharska, T Kowalczyk, R Zajdel |
International journal of molecular sciences | 2021 |
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Effect of 1-MHz ultrasound on the proinflammatory interleukin-6 secretion in human keratinocytes
S Giantulli, E Tortorella, F Brasili, S Scarpa, B Cerroni, G Paradossi, A Bedini, S Morrone, I Silvestri, F Domenici |
Scientific Reports | 2021 |
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The Immune Functions of Keratinocytes in Skin Wound Healing
M Piipponen, D Li, NX Landén |
International journal of molecular sciences | 2020 |
