Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung

Beitragende

  • George Hajishengallis - , University of Pennsylvania (Autor:in)
  • Xiaofei Li - , University of Pennsylvania (Autor:in)
  • Kimon Divaris - , University of North Carolina at Chapel Hill (Autor:in)
  • Triantafyllos Chavakis - , Institut für Klinische Chemie und Laboratoriumsmedizin (Autor:in)

Abstract

Periodontitis is bidirectionally associated with systemic inflammatory disorders. The prevalence and severity of this oral disease and linked comorbidities increases with aging. Here, we review two newly emerged concepts, trained innate immunity (TII) and clonal hematopoiesis of indeterminate potential (CHIP), which together support a potential hypothesis on how periodontitis affects and is affected by comorbidities and why the susceptibility to periodontitis and comorbidities increases with aging. Given that chronic diseases are largely triggered by the action of inflammatory immune cells, modulation of their bone marrow precursors, the hematopoietic stem and progenitor cells (HSPCs), may affect multiple disorders that emerge as comorbidities. Such alterations in HSPCs can be mediated by TII and/or CHIP, two non-mutually exclusive processes sharing a bias for enhanced myelopoiesis and production of innate immune cells with heightened proinflammatory potential. TII is a state of elevated immune responsiveness based on innate immune (epigenetic) memory. Systemic inflammation can initiate TII in the bone marrow via sustained rewiring of HSPCs, which thereby display a skewing toward the myeloid lineage, resulting in generation of hyper-reactive or “trained” myeloid cells. CHIP arises from aging-related somatic mutations in HSPCs, which confer a survival and proliferation advantage to the mutant HSPCs and give rise to an outsized fraction of hyper-inflammatory mutant myeloid cells in the circulation and tissues. This review discusses emerging evidence that supports the notion that TII and CHIP may underlie a causal and age-related association between periodontitis and comorbidities. A holistic mechanistic understanding of the periodontitis-systemic disease connection may offer novel diagnostic and therapeutic targets for treating inflammatory comorbidities.

Details

OriginalspracheEnglisch
Seiten (von - bis)215-230
Seitenumfang16
FachzeitschriftPeriodontology 2000
Jahrgang89
Ausgabenummer1
PublikationsstatusVeröffentlicht - Juni 2022
Peer-Review-StatusJa

Externe IDs

PubMed 35244943

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • aging, clonal hematopoiesis, comorbidities, hematopoietic stem cells, periodontitis, trained immunity

Bibliotheksschlagworte