{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:50:50Z","timestamp":1792302650248,"version":"4.4.0"},"reference-count":132,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC\/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology.<\/jats:p>","DOI":"10.3390\/ijms27083363","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:56:07Z","timestamp":1775724967000},"page":"3363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immuno-Mechanical Signaling Network Integration in Temporomandibular Joint Pathology: A TMID Conceptual Framework"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4386-7604","authenticated-orcid":false,"given":"Hyoung-Jun","family":"Kim","sequence":"first","affiliation":[{"name":"OFP Dental Clinic, Seoul 06237, Republic of Korea"},{"name":"Department of Oral Medicine and Oral Diagnosis, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hong","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoultop Dental Clinic, Seoul 12218, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Il","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Oral Diagnosis, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Yeon Dental Clinic, Seoul 04363, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","article-title":"Tolerance, danger, and the extended family","volume":"12","author":"Matzinger","year":"1994","journal-title":"Annu. 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