Chronic inflammation impacting hematopoiesis and immune cell function

Chronic inflammation exerts pervasive effects on hematopoiesis and immune cell function through shifting the phenotype of stem and progenitor cells, reshaping the tissue/tumor microenvironment, and impacting the cellular dynamics of hematopoietic and immune cells. Such effects profoundly influence the clinical efficacy of hematopoietic stem cell therapies (HSCT, e.g. bone marrow transplantation) and immune cell therapies (ICT, e.g. adoptive T-cell therapy). Persistent inflammatory signals derived from tumors, infections, metabolic dysfunction, autoimmunity, aging, or environmental exposures can skew lineage commitment, alter stem and progenitor cell fate, and impair immune cell activation and persistence. These alterations contribute to hematologic dysfunction, clonal hematopoiesis, dysregulated innate and adaptive responses, and eventual hematopoietic failure or immune deficiency.Importantly, emerging evidence suggests a bidirectional relationship between chronic inflammation and clonal hematopoiesis. Systemic and bone marrow–localized inflammation may promote the selection and expansion of hematopoietic clones, while clonal hematopoiesis may in turn sustain or amplify local and systemic inflammation, creating a self-reinforcing inflammation–clonal hematopoiesis feedback loop. In HSCT and ICT, these inflammatory and clonal alterations may contribute to frequent clinical issues such as impaired engraftment, clonal expansion, hematopoietic dysfunction, and CAR-T/TCR-T cell exhaustion. Emerging single-cell, multi-omics, and spatial profiling studies reveal complex crosstalk among systemic inflammation, the tissue/tumor environment, the bone marrow niche, and the adaptive immune system. Timely and comprehensive understanding of these interactions is of interest to both biological and clinical audiences. Inflammatory signals from these diverse sources shape pathological hematopoietic and immune phenotypes associated with chronic inflammation and are potential targets for improving HSCT and ICT therapeutic efficacy. Evidence supporting these concepts is dispersed across a large variety of disease settings, while emerging studies in clonal hematopoiesis, gene-edited HSCT, and ICT are gaining increasing attention from biological and clinical audiences.This Research Topic aims to collect original research and reviews to provide comprehensive, unified coverage of these interconnected processes, filling the gap between descriptive evidence of inflammation-driven dysfunction and actionable, mechanism-based strategies to improve therapy in inflamed hosts. We will solicit mechanistic studies with clinical relevance, including single-cell and spatial multi-omics linked to functional assays and lineage tracing, well-characterized preclinical models that mimic clinically relevant inflammatory milieus, and human studies or trial data correlating inflammatory and clonal signatures with disease and therapeutic outcomes. Review articles that connect dispersed evidence from experimental studies and clinical trials to mechanistic explanations and/or therapeutic potential in chronic inflammation are also encouraged.This Research Topic aims to bridge mechanistic biology and clinical translation by focusing on how chronic inflammation alters hematopoietic stem and progenitor cell (HSPC) biology and undermines the efficacy of HSCT and ICT. We invite original research, reviews, and short reports that:- Elucidate molecular and cellular pathways by which tumor-, infection-, metabolic-, autoimmune-, age-, or environment-driven inflammatory signals influence HSPC phenotype, clonal hematopoiesis, lineage bias, self-renewal, and differentiation.- Investigate the types and mechanisms of clonal hematopoiesis associated with different chronic inflammatory conditions and define the bidirectional interactions between clonal hematopoiesis and local bone marrow and systemic inflammation.- Define mechanisms linking inflammatory remodeling of tissue and tumor microenvironments to impaired engraftment, clonal expansion, or hematopoietic failure after HSCT.- Characterize causes of ICT dysfunction, including impaired activation, poor persistence, or exhaustion of CAR-T/TCR-T and other adoptive cell products in inflamed hosts.- Apply single-cell, spatial, and multi-omic approaches alongside functional assays and lineage tracing to map how progenitor-to-effector transitions are altered by chronic inflammation.- Integrate human study data with preclinical models to identify predictive biomarkers of disease and therapy outcome.- Evaluate interventions (e.g. pharmacologic, metabolic, niche-targeted, or conditioning regimen–based) designed to improve HSCT/ICT success in inflamed settings and, where appropriate, interrupt inflammation–clonal hematopoiesis feedback loops.Clinical or translational studies with clear mechanistic links are especially encouraged. Studies that are unrelated to immunity or immune-related mechanisms of inflammation are out of scope for this section. Topic editors: Helong Gary Zhao, Helen A. Papadaki, Yapeng Su, Stanley C. Lee Source: https://www.frontiersin.org/research-topics/86184/chronic-inflammation-impacting-hematopoiesis-and-immune-cell-function