{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:34:00Z","timestamp":1789724040933,"version":"4.0.1"},"reference-count":121,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Historically, immunological memory was considered an exclusive feature of adaptive immunity. However, innate immune cells have recently been shown to record and maintain epigenetically imprinted memory of earlier infectious or inflammatory challenges. In the bone marrow, hematopoietic stem and progenitor cells (HSPCs) can also build inflammatory memory, which leads to trained myelopoiesis, that is, the production of high numbers of myeloid cells with increased inflammatory responsiveness to future challenges. Another condition affecting HSPCs and causing overproduction of leukocytes with increased inflammatory responsiveness is clonal hematopoiesis of indeterminate potential (CHIP). Occurring at high prevalence in the elderly, CHIP is driven predominantly by somatic mutations in genes encoding epigenetic modifiers, hence altering the epigenetic landscape of hematopoietic progenitors and their mature progeny. Although trained myelopoiesis and CHIP may have beneficial effects, they can also act in a maladaptive context and aggravate inflammation in periodontal disease and systemic conditions, thereby forming a common mechanistic basis for inflammatory comorbidities. This review discusses recent experimental and clinical evidence on the mechanisms and implications of maladaptive hematopoiesis\u2014due to trained myelopoiesis or CHIP\u2014\u2010in periodontitis and associated inflammatory comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Traditionally, immune memory\u2014the ability to \u201cremember\u201d past infections\u2014was thought to be limited to the adaptive immune system. But recent discoveries show that even the more ancient part of the immune system, the innate immune system, can also develop a form of memory. This memory is stored through changes in how genes are regulated, and it begins in the bone marrow. There, blood\u2010forming stem cells can be \u201ctrained\u201d by previous infection or inflammation to produce more immune cells that respond more aggressively to future threats, a process known as trained myelopoiesis. An analogous process happens in a condition called clonal hematopoiesis of indeterminate potential (CHIP), which is common in older adults. In CHIP, mutations in certain genes cause the bone marrow to overproduce immune cells that are overly reactive. While trained myelopoiesis and CHIP may exert protective effects, they can also backfire. Both trained myelopoiesis and CHIP have been linked to increased inflammation in gum disease and associated systemic conditions. This review explores how bone marrow\u2013driven changes in the production and activity of immune cells may contribute to a shared underlying cause of multiple inflammatory disorders and why understanding these processes could open new doors for treatment and prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70040","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T08:51:33Z","timestamp":1766739093000},"page":"175-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Epigenetic inflammatory memory and periodontal disease: Mechanisms and clinical significance for comorbidities"],"prefix":"10.1002","volume":"97","author":[{"given":"George","family":"Hajishengallis","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Sciences Penn Dental Medicine, University of Pennsylvania  Philadelphia Pennsylvania 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