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

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

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

Original languageEnglish
Pages (from-to)215-230
Number of pages16
JournalPeriodontology 2000
Volume89
Issue number1
Publication statusPublished - Jun 2022
Peer-reviewedYes

External IDs

PubMed 35244943

Keywords

ASJC Scopus subject areas

Keywords

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

Library keywords