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Peripheral neuroimmune crosstalk occurs through multiple anatomical pathways, including autonomic efferents, sympathetic circuits, and sensory afferents that detect tissue perturbation. Among these pathways, the vagus nerve has emerged as a prominent conduit for neuroimmune communication, integrating homeostatic and inflammatory cues to shape both local and systemic immune responses. In this review, we examine the structural and functional organization of vagal neuroimmune circuits, highlighting how vagal sensory neurons detect and encode inflammatory cues and how defined vagal pathways modulate immune responses in health and disease. We also discuss recent advances in bioelectronic medicine for treating chronic inflammatory disorders, emphasizing both therapeutic promise and current challenges that remain for clinical translation. Defining the cellular specificity and physiology of vagal neuroimmune circuits will be essential for developing precise neuromodulation strategies to treat inflammatory and autoimmune disorders.<\/jats:p>","DOI":"10.1084\/jem.20260135","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:20:58Z","timestamp":1787811658000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Vagal neuroimmune circuits in inflammation and immunity"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-2761","authenticated-orcid":true,"given":"Tom\u00e1s S.","family":"Huerta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Blavatnik Institute, Harvard Medical School 1 Department of Immunology, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-6314","authenticated-orcid":true,"given":"Kevin J.","family":"Tracey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bxt4m23","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health 2 Laboratory of Biomedical Sciences, , Manhasset, NY,","place":["USA"]},{"name":"The Elmezzi Graduate School of Molecular Medicine 3 , Manhasset, NY,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/01ff5td15","id-type":"ROR","asserted-by":"publisher"}],"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hofstra University 4 , Hempstead, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-4841","authenticated-orcid":true,"given":"Isaac M.","family":"Chiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Blavatnik Institute, Harvard Medical School 1 Department of Immunology, , Boston, MA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"The Gene Lay Institute of Immunology and Inflammation of Brigham and Women\u2019s Hospital, Massachusetts General Hospital, and Harvard Medical School 5 , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5592-4276","authenticated-orcid":true,"given":"Eric H.","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bxt4m23","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health 2 Laboratory of Biomedical Sciences, , Manhasset, NY,","place":["USA"]},{"name":"The Elmezzi Graduate School of Molecular Medicine 3 , Manhasset, NY,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/01ff5td15","id-type":"ROR","asserted-by":"publisher"}],"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hofstra University 4 , Hempstead, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"2026092509470059600_bib1","doi-asserted-by":"publisher","first-page":"bqab029","DOI":"10.1210\/endocr\/bqab029","article-title":"Monitoring in vivo neural activity to understand gut-brain signaling","volume":"162","author":"Alhadeff","year":"2021","journal-title":"Endocrinology"},{"key":"2026092509470059600_bib2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ads6243","article-title":"Vagal TRPV1+ sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics","volume":"10","author":"Almanzar","year":"2025","journal-title":"Sci. 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