Systems Approaches to Understanding Self-tolerance and Immunotherapy Responses

A cornerstone of the immune system is its ability to maintain self-tolerance. This defense network orchestrates effector responses against pathogenic threats or harmful host components. Disruption in this delicate balance can occasionally cause the immune system to target self-tissues, leading to auto-inflammation. Recent studies underscore the pivotal role of the neuro-immune axis and circadian clock genes in modulating immune responses, with their dysfunction contributing to autoimmune pathogenesis. At the cellular level, aberrant extra-follicular and germinal center responses resulting from altered T-B synergy and B cell activation contribute to the production of pathogenic autoantibodies. Advances in immunotherapies, including targeted biologics and immune modulators, provide new avenues to restore immune homeostasis and ameliorate autoimmune conditions.

Despite efforts to unveil the pathogenesis of autoimmune conditions, the immunological mechanisms underlying these disorders remain poorly understood. As cell-cell interactions and their dynamics mediate immune responses, mathematical models and systems approaches are critical for addressing immune dysregulation across scales, from cellular interactions to system-wide effects. Modern systems immunology, integrating quantitative and experimental methods, promises to significantly enhance our understanding of self-tolerance and guide the development of novel therapeutics for immune disorders. In this Research Topic, we aim to elucidate aberrant adaptive immune responses of T cells and B cells, as well as their neuro-immune and circadian regulation. We are particularly focused on investigating the mechanisms behind the breakdown of self-tolerance through systems approaches. This includes modeling immune responses from the immune synapse to antibody responses and exploring predictive modeling of potential novel therapeutics, including emerging bi- and tri-specific antibodies and CAR-T cell therapies.

This Research Topic accepts Original Research, Perspective, Systematic Review, Hypothesis and Theory, Methods, Technology and Code. We welcome manuscripts focusing on, but not limited to, the following sub-topics:

• Quantitative models of T cell and B cell response

• Autoantibody responses: Modeling extra-follicular and germinal center responses

• Role of T cells–B cells cross-communication in self-tolerance

• Role of neuro-immune and circadian regulation

• Quantitative models of immunotherapies and modern biologics



Topic Editor Michael L Dustin is Founder at GranzaBio and consultant for Labgenius and Molecular Partners. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Self-tolerance and emergence of autoimmunity, Computational and Systems Biology, Immune Signaling, Quantitative models, Immunotherapy.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.