Frontiers Launches Research Topic on Cellular Dysregulation in Autoimmune and Autoinflammatory Diseases, Seeking Novel Therapeutic Strategies
Key Insights
Frontiers (search) has opened a new Research Topic focused on cellular dysregulation mechanisms driving autoimmune and autoinflammatory diseases beyond traditional immune-centric models.
The initiative seeks to integrate cell-intrinsic alterations—such as proteostasis defects, metabolic imbalance, and epigenetic remodeling—with microenvironmental signals to understand disease pathogenesis.
Submissions are encouraged across diverse formats including Original Research, Reviews, and Clinical Trials, with emphasis on single-cell omics, spatial omics, and systems biology approaches.
A new Research Topic launched by Frontiers (search) in Immunology aims to reframe the understanding of autoimmune and autoinflammatory diseases by shifting focus from classical immune dysregulation toward broader cellular homeostasis disruptions. The initiative, titled "Cellular Dysregulation in Autoimmune and Autoinflammatory Diseases: Emerging Mechanisms and Therapeutic Opportunities," calls for submissions that explore how cell-intrinsic and cell-extrinsic alterations drive disease pathogenesis across both immune and non-immune compartments.
The Research Topic challenges the traditional dichotomy that separates autoimmune disorders—viewed as adaptive immune dysregulation—from autoinflammatory conditions attributed to innate immune overactivation. Instead, the editors argue that these diseases share common roots in disrupted cellular programs, including aberrant stress-adaptive responses, defective protein homeostasis, metabolic imbalance, epigenetic remodeling, persistent inflammasome activation, dysregulated senescence programs, and maladaptive trained immunity.
A Framework Centered on Cellular Homeostasis
The editorial team emphasizes that intercellular communication within complex tissue microenvironments—mediated by paracrine signaling and extracellular vesicles—plays a critical role in amplifying and sustaining immune dysregulation and inflammatory responses. This evolving perspective calls for a more integrated understanding of disease mechanisms, centered on cell-intrinsic and extrinsic alterations as unifying frameworks across autoimmune and autoinflammatory conditions.
"Despite important advances in the understanding of immune-mediated pathways and diseases, many mechanistic aspects underlying autoimmune and autoinflammatory disorders remain poorly defined, limiting the development of effective and targeted therapies," the editors state in the Research Topic description.
Technological Advances Enabling High-Resolution Investigation
The Research Topic highlights recent technological advances—including single-cell omics, spatial omics, and systems biology approaches—as offering "unprecedented opportunities to dissect these processes at high resolution." By bringing together fundamental and translational research, the initiative aims to identify novel pathogenic pathways and uncover innovative therapeutic strategies targeting not only immune responses but also broader cellular dysfunctions.
Submissions are particularly encouraged in several key areas: dysregulation of non-immune and immune cells contributing to disease pathogenesis; cell-intrinsic pathogenic mechanisms; the role of the tissue microenvironment and cell-extrinsic mechanisms; single-cell and spatial omics approaches; mechanisms linking chronic inflammation to tissue damage and impaired repair; pathways linking immune dysregulation to tissue damage; identification of novel biomarkers; and emerging regenerative and resolution-based therapeutic strategies beyond classical immune modulation.
Translational Focus and Patent Disclosure
The Research Topic accepts submissions in diverse formats including Brief Research Report, Case Report, Clinical Trial, Original Research, Review, Systematic Review, Perspective, and Study Protocol, among others. All published articles will undergo rigorous external peer review and may be subject to publication fees.
Notably, manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases without robust validation—either through clinical cohorts or biological validation in vitro or in vivo—are considered out of scope. Cost-effectiveness studies are also not accepted.
Topic Editor Raffaella Molteni disclosed a pending patent (PCT/IB2024/060412) titled "Means and Methods for Genetic Modification of UBA1 (search)," filed on October 23, 2024, with inventors S. Ferrari, M. Fiumara, L. Naldini, R. Molteni, and G. Cavalli. The patent highlights the translational ambitions underlying this Research Topic and the potential for therapeutic innovation targeting cellular dysregulation pathways.
The editors particularly encourage studies that bridge mechanistic insights with translational relevance and therapeutic innovation, with the ultimate goal of fostering "more precise and effective interventions" for patients affected by autoimmune and autoinflammatory conditions.