{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:46:50Z","timestamp":1785923210462,"version":"3.56.0"},"reference-count":83,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Xizang Autonomous Region","award":["XZ202601ZR0139"],"award-info":[{"award-number":["XZ202601ZR0139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Beyond its canonical role as the principal inhibitory neurotransmitter in the central nervous system (CNS), peripheral GABAergic signaling has emerged as an important regulator of skin barrier immunity and tissue homeostasis. This review synthesizes current evidence on the expression, distribution, and function of both GABA-A and GABA-B receptors in keratinocytes, fibroblasts, melanocytes, sensory neurons, and cutaneous immune cells, including Langerhans cells, macrophages, mast cells, and T lymphocytes. Particular emphasis is placed on how GABAergic signaling regulates ion transport, calcium dynamics, epidermal differentiation, and immune homeostasis through coordinated interactions with ion channels within the broader cutaneous neuro-immuno-endocrine network. We further discuss evidence supporting the role of cutaneous GABAergic signaling in maintaining barrier integrity, modulating inflammatory responses, and contributing to skin\u2013brain communication within the broader cutaneous neuro-immuno-endocrine network under physiological and pathological conditions. Finally, we summarize the therapeutic potential of targeting peripheral GABAergic pathways in atopic dermatitis, psoriasis, chronic pruritus, photoaging, and other stress-associated dermatoses, highlighting their promise as novel therapeutic strategies in precision dermatology.<\/jats:p>","DOI":"10.3390\/ijms27156944","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Brain: GABAergic Signaling as a Peripheral Modulator of Skin Barrier Immunity"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruoyu","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Dermatology, West China Hospital Tibet Hospital, Sichuan University, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3061-5749","authenticated-orcid":false,"given":"Wei","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Cosmetic Evaluation Center of West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1523-1747.2003.12359.x","article-title":"Barrier Function of the Skin: \u201cLa Raison d\u2019\u00catre\u201d of the Epidermis","volume":"121","author":"Madison","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1600-0625.2008.00786.x","article-title":"The skin: An indispensable barrier","volume":"17","author":"Proksch","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41574-025-01107-x","article-title":"Neuro\u2013immuno\u2013endocrinology of the skin: How environment regulates body homeostasis","volume":"21","author":"Slominski","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1152\/physrev.00026.2005","article-title":"Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ","volume":"86","author":"Roosterman","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/physrev.2000.80.3.979","article-title":"Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress","volume":"80","author":"Slominski","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-19683-6_1","article-title":"Sensing the Environment: Regulation of Local and Global Homeostasis by the Skin\u2019s Neuroendocrine System","volume":"212","author":"Slominski","year":"2012","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.4049\/jimmunol.150.10.4478","article-title":"Substance P selectively activates TNF-alpha gene expression in murine mast cells","volume":"150","author":"Ansel","year":"1993","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin Gene-Related Peptide: Physiology and Pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1210\/er.2012-1092","article-title":"Key Role of CRF in the Skin Stress Response System","volume":"34","author":"Slominski","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s11154-016-9369-9","article-title":"Neuroendocrinology of the skin","volume":"17","author":"Theoharides","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_11","first-page":"457","article-title":"Neuroendocrinology of the Skin1","volume":"21","author":"Slominski","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The capsaicin receptor: A heat-activated ion channel in the pain pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, H., Choi, M.R., Jeon, S.H., Jang, Y., and Yang, Y.D. (2024). Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052756"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1124\/pr.108.00505","article-title":"International Union of Pharmacology. LXX. Subtypes of \u03b3-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update","volume":"60","author":"Olsen","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/nn.3144","article-title":"Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology","volume":"15","author":"Chiu","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00281-018-0675-z","article-title":"Skin neurogenic inflammation","volume":"40","author":"Choi","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/j.1600-0625.2010.01076.x","article-title":"Anti-inflammatory effects of the GABAB receptor agonist baclofen in allergic contact dermatitis","volume":"19","author":"Duthey","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175910","DOI":"10.1016\/j.ejphar.2023.175910","article-title":"Anti-proliferative and anti-inflammatory effects of the application of baclofen cream, a GABAB receptor agonist, on skin inflammation in mice","volume":"955","author":"Oliveira","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00403-010-1052-5","article-title":"GABA and GABAA receptor expression on immune cells in psoriasis: A pathophysiological role","volume":"302","author":"Nigam","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7696(02)13011-7","article-title":"GABA and GABA Receptors in the Central Nervous System and Other Organs","volume":"213","author":"Watanabe","year":"2002","journal-title":"Int. Rev. Cytol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1073\/pnas.0915139107","article-title":"Inhibitory role for GABA in autoimmune inflammation","volume":"107","author":"Bhat","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1038\/sj.bjp.0706443","article-title":"GABA and glycine as neurotransmitters: A brief history","volume":"147","author":"Bowery","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbagen.2006.09.017","article-title":"GABA-synthesizing enzyme, GAD67, from dermal fibroblasts: Evidence for a new skin function","volume":"1770","author":"Ito","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.0022-202X.2004.23313.x","article-title":"The Osmolyte Strategy of Normal Human Keratinocytes in Maintaining Cell Homeostasis","volume":"123","author":"Warskulat","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","first-page":"482","article-title":"Organic osmolytes increase expression of specific tight junction proteins in skin and alter barrier function in keratinocytes","volume":"184","author":"Foster","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1152\/physrev.00015.2010","article-title":"The Dynamic Modulation of GABAAReceptor Trafficking and Its Role in Regulating the Plasticity of Inhibitory Synapses","volume":"91","author":"Vithlani","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1007\/s00018-021-03881-z","article-title":"GABAergic signaling by cells of the immune system: More the rule than the exception","volume":"78","author":"Bhandage","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nrn3249","article-title":"Regulation of neuronal GABAB receptor functions by subunit composition","volume":"13","author":"Gassmann","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/(SICI)1096-9861(19970421)380:4<520::AID-CNE8>3.0.CO;2-3","article-title":"Immunocytochemical localization of the GABA(C) receptor rho subunits in the cat, goldfish, and chicken retina","volume":"380","author":"Koulen","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"ref_31","first-page":"108759","article-title":"Peripheral GABAA receptors\u2013Physiological relevance and therapeutic implications","volume":"266","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hyland, N.P., and Cryan, J.F. (2010). A Gut Feeling about GABA: Focus on GABAB Receptors. Front. Pharmacol., 01.","DOI":"10.3389\/fphar.2010.00124"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41564-018-0307-3","article-title":"GABA-modulating bacteria of the human gut microbiota","volume":"4","author":"Strandwitz","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.tins.2004.03.005","article-title":"Tonically active GABAA receptors: Modulating gain and maintaining the tone","volume":"27","author":"Semyanov","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1046\/j.1523-1747.2002.19504.x","article-title":"\u03b3-Aminobutyric Acid (A) Receptor Agonists Accelerate Cutaneous Barrier Recovery and Prevent Epidermal Hyperplasia Induced by Barrier Disruption","volume":"119","author":"Denda","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1080\/09168451.2017.1290518","article-title":"GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs)","volume":"81","author":"Uehara","year":"2017","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1158\/2159-8290.CD-23-0389","article-title":"GABA Regulates Electrical Activity and Tumor Initiation in Melanoma","volume":"13","author":"Tagore","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.neuropharm.2010.11.007","article-title":"An intrinsic GABAergic system in human lymphocytes","volume":"60","author":"Dionisio","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuropharm.2008.07.045","article-title":"GABAA receptors: Subtypes provide diversity of function and pharmacology","volume":"56","author":"Olsen","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Xu, X., Yu, C., Xu, L., and Xu, J. (2022). Emerging roles of keratinocytes in nociceptive transduction and regulation. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.982202"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jin, Y., Korol, S.V., Jin, Z., Barg, S., and Birnir, B. (2013). In Intact Islets Interstitial GABA Activates GABAA Receptors That Generate Tonic Currents in \u03b1-Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067228"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1089\/wound.2022.0128","article-title":"Maintaining and Restoring Gradients of Ions in the Epidermis: The Role of Ion and Water Channels in Acute Cutaneous Wound Healing","volume":"12","author":"Mai","year":"2023","journal-title":"Adv. Wound Care"},{"key":"ref_43","first-page":"G453","article-title":"A novel role of intestine epithelial GABAergic signaling in regulating intestinal fluid secretion","volume":"303","author":"Li","year":"2012","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1042\/bj20031089","article-title":"Ca2+ waves in keratinocytes are transmitted to sensory neurons: The involvement of extracellular ATP and P2Y2 receptor activation","volume":"380","author":"Koizumi","year":"2004","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1586\/eem.12.34","article-title":"Calcium regulation of keratinocyte differentiation","volume":"7","author":"Bikle","year":"2012","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1600-0625.2006.00539.x","article-title":"Tight junction proteins in keratinocytes: Localization and contribution to barrier function","volume":"16","author":"Yuki","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.4062\/biomolther.2023.085","article-title":"The Effect of \u03b3-Aminobutyric Acid Intake on UVB- Induced Skin Damage in Hairless Mice","volume":"31","author":"Zhao","year":"2023","journal-title":"Biomol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12934-023-02264-2","article-title":"Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota","volume":"22","author":"Kaur","year":"2023","journal-title":"Microb. Cell Factories"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nature05662","article-title":"Mechanisms of sensory transduction in the skin","volume":"445","author":"Lumpkin","year":"2007","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000343173","article-title":"Activation of TRPV4 Strengthens the Tight-Junction Barrier in Human Epidermal Keratinocytes","volume":"26","author":"Akazawa","year":"2012","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e21074","DOI":"10.7554\/eLife.21074","article-title":"Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes","volume":"6","author":"Moroni","year":"2017","journal-title":"eLife"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejcb.2008.10.002","article-title":"Functional interaction of the cation channel transient receptor potential vanilloid 4 (TRPV4) and actin in volume regulation","volume":"88","author":"Becker","year":"2009","journal-title":"Eur. J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/jn.1997.78.1.31","article-title":"Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons","volume":"78","author":"Oyelese","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1242\/jcs.002741","article-title":"CLIC4 mediates and is required for Ca2+-induced keratinocyte differentiation","volume":"120","author":"Suh","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10974","DOI":"10.1523\/JNEUROSCI.2619-04.2004","article-title":"Acid-Induced Pain and Its Modulation in Humans","volume":"24","author":"Jones","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.conb.2013.11.004","article-title":"GABA actions and ionic plasticity in epilepsy","volume":"26","author":"Kaila","year":"2014","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrn2993","article-title":"Molecular mechanisms of mechanotransduction in mammalian sensory neurons","volume":"12","author":"Delmas","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.yjmcc.2012.10.016","article-title":"TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals","volume":"54","author":"Adapala","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ebiom.2018.03.019","article-title":"GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes","volume":"30","author":"Bhandage","year":"2018","journal-title":"eBioMedicine"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Shan, Y., Zhao, J., Zheng, Y., Guo, S., Schrodi, S.J., and He, D. (2023). Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1114350"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.2741\/4539","article-title":"The immunological function of GABAergic system","volume":"22","author":"Peng","year":"2017","journal-title":"Front. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00726-011-1193-7","article-title":"GABA is an effective immunomodulatory molecule","volume":"45","author":"Jin","year":"2013","journal-title":"Amino Acids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/15384101.2024.2340912","article-title":"Role of \u03b23 subunit of the GABA type A receptor in triple negative breast cancer proliferation, migration, and cell cycle progression","volume":"23","author":"Bundy","year":"2024","journal-title":"Cell Cycle"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/stem.573","article-title":"GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors","volume":"29","author":"Cesetti","year":"2011","journal-title":"Stem Cells"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Poterlowicz, K., Yarker, J.L., Malashchuk, I., Lajoie, B.R., Mardaryev, A.N., Gdula, M.R.A., Sharov, A., Kohwi-Shigematsu, T.A., Botchkarev, V., and Fessing, M.Y. (2017). 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006966"},{"key":"ref_66","first-page":"1661","article-title":"Wound healing activity of gamma-aminobutyric Acid (GABA) in rats","volume":"17","author":"Han","year":"2007","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1152\/physrev.00018.2011","article-title":"Role of Ion Channels and Transporters in Cell Migration","volume":"92","author":"Schwab","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200110122","article-title":"Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice","volume":"156","author":"Furuse","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_69","first-page":"G851","article-title":"Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier","volume":"298","author":"Karczewski","year":"2010","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7314","DOI":"10.1111\/febs.16174","article-title":"Junctional complexes in epithelial cells: Sentinels for extracellular insults and intracellular homeostasis","volume":"289","author":"Fu","year":"2021","journal-title":"FEBS J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jdermsci.2017.06.003","article-title":"Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin","volume":"87","author":"Bitschar","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"121984","DOI":"10.1016\/j.lfs.2023.121984","article-title":"Activation of GABA receptor attenuates intestinal inflammation by modulating enteric glial cells function through inhibiting NF-\u03baB pathway","volume":"329","author":"Deng","year":"2023","journal-title":"Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.autrev.2015.07.011","article-title":"Immunological GABAergic interactions and therapeutic applications in autoimmune diseases","volume":"14","author":"Glinka","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jaci.2017.02.001","article-title":"Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis","volume":"140","author":"Cevikbas","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Marionnet, C., Pierrard, C., Lejeune, F., Sok, J., Thomas, M., and Bernerd, F. (2010). Different Oxidative Stress Response in Keratinocytes and Fibroblasts of Reconstructed Skin Exposed to Non Extreme Daily-Ultraviolet Radiation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012059"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Charnvanich, D., Singpanna, K., and Panapisal, V. (2024). Formulation and Optimization of Nanoemulsions Loaded with Gamma\u2212Aminobutyric Acid (GABA) for Dermatological Application: Assessing Skin Permeation and Penetration Enhancement. Cosmetics, 11.","DOI":"10.3390\/cosmetics11010019"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/hdi.13175","article-title":"Effectiveness of topical gabapentin cream in treating pruritus in dialysis patients: A randomized controlled trial","volume":"28","author":"Faghihi","year":"2024","journal-title":"Hemodial. Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11916-017-0615-y","article-title":"Topical Treatments for Localized Neuropathic Pain","volume":"21","author":"Casale","year":"2017","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s13555-021-00513-z","article-title":"Gabapentinoids for Pruritus in Older Adults: A Narrative Review","volume":"11","author":"Sreekantaswamy","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1016\/j.ekir.2025.06.037","article-title":"Meta-Analysis of Randomized Controlled Trials on Gamma-Aminobutyric Acid Analogues and Opioid-Based Therapies for CKD-Associated Pruritus","volume":"10","author":"Wathanavasin","year":"2025","journal-title":"Kidney Int. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.jid.2024.02.006","article-title":"Genetic Tools for Cell Lineage Tracing and Profiling Developmental Trajectories in the Skin","volume":"144","author":"Nathans","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.jaci.2020.01.042","article-title":"Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis","volume":"145","author":"He","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00656997","article-title":"Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches","volume":"391","author":"Hamill","year":"1981","journal-title":"Pfl\u00fcgers Arch."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:17:25Z","timestamp":1785921445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,2]]},"references-count":83,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156944"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156944","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,2]]}}}