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Tissue\u2010resident macrophages exhibit a continuous functional spectrum rather than rigid binary M1\/M2 subsets, and their dynamic reprogramming critically shapes inflammatory onset, perpetuation and resolution; however, conventional experimental approaches cannot readily provide causal, high spatiotemporal\u2010resolution evidence for neuron\u2013macrophage communication in intact skin. Optogenetics combined with intravital in\u00a0vivo calcium imaging has emerged as a powerful integrated platform to precisely manipulate sensory neuronal activity and simultaneously record real\u2010time calcium signalling dynamics in macrophages. Herein, we review recent advances using this toolkit in psoriasiform skin inflammation. Optogenetic activation of nociceptive sensory neurons triggers rapid macrophage calcium transients primarily mediated by neuropeptide calcitonin gene\u2010related peptide (CGRP). Chronic optogenetic neuronal stimulation is sufficient to initiate psoriasiform lesions, whereas optogenetic silencing can reverse established skin inflammation. Downstream calcium\u2010CaMKII\u2010NF\u2010\u03baB\/MAPK cascades drive pro\u2010inflammatory macrophage activation, while sympathetic norepinephrine\u2010dependent \u03b22\u2010adrenergic receptor signalling provides homeostatic negative feedback. A spatiotemporal calcium\u2010wave model further explains focal plaque formation. We also discuss translational bottlenecks for optogenetic techniques and potential therapeutic targets targeting sensory neuron\u2013macrophage axis. Finally, we highlight future multimodal research directions bridging pre\u2010clinical mechanistic findings and clinical translation for psoriasis and other neuro\u2010immune inflammatory skin diseases.<\/jats:p>","DOI":"10.1111\/exd.70361","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:17:55Z","timestamp":1789546675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optogenetic Dissection of Sensory Neuron\u2013Macrophage Interactions in Psoriasiform Skin Inflammation: Advances Based on In\u00a0Vivo Calcium Imaging Techniques"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4313-6918","authenticated-orcid":false,"given":"Peiyao","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2594-7380","authenticated-orcid":false,"given":"Liuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Hubei University of Chinese Medicine  Wuhan China"},{"name":"Department of Dermatology, Wuhan Integrated Traditional Chinese and Western Medicine Hospital Affiliated With Hubei University of Chinese Medicine  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2025.07.018"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006607\u20102"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800395RR"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.787565"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010025\u201002095\u20100"},{"key":"e_1_2_16_7_1","first-page":"75","article-title":"Correlation of CD4+\u0422 Lymphocytes Activation With Interleukin Il\u20109, Il\u201017, Il\u2010 22 Profiles in the Peripheral Blood of Patients With Plaque Psoriasis","volume":"66","author":"Mitskevich N.","year":"2021","journal-title":"Georgian Medical 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