Frontiers in Immunology opens a call centered on immune tolerance in tissue repair
Tissue repair depends on an immune system that can do two things at once: clear injury, debris, and pathogens, then step back quickly enough to allow rebuilding. Frontiers in Immunology has opened a Research Topic devoted to that balancing act, with a specific focus on how immune regulation and tolerance shape regeneration across organ systems.
The topic is built around a familiar paradox in translational immunology. The same inflammatory machinery that prevents infection and clears damaged tissue can also sabotage regeneration when it lingers too long or becomes misdirected. In that setting, repair gives way to scar formation, chronic inflammation, autoimmunity, graft rejection, or even tumor growth. The call for papers is designed to move the field beyond isolated organ-specific observations and toward shared principles that explain how regulatory immune circuits are assembled, maintained, and eventually lost.
Regulatory cells sit at the center of the repair response
The scope of the Research Topic places myeloid-derived suppressor cells, regulatory T cells, tolerogenic macrophages, natural killer cell subsets, and other regulatory populations at the center of the discussion. These cells are presented not as passive bystanders but as active architects of the microenvironment that permits proliferating and remodeling tissues to recover without triggering excess immune injury.
In liver regeneration, recent work has shown that myeloid-derived suppressor cells expand after injury, interact with natural killer cells, and correlate with cellular proliferation. That pattern offers a useful example of the kind of immune choreography the topic seeks to capture. The liver is not alone. Similar regulatory circuits are now being described in the heart, vasculature, intestine, skin, and transplanted organs, suggesting that regenerative immunity may share conserved logic even when the tissue context changes.
A single regulatory pathway rarely decides the outcome. Repair emerges from cell-cell communication, local cytokine tone, and the timing of immune suppression relative to proliferation and remodeling.
The biology of repair turns when tolerance fails
The editorial framing of the topic is explicit about the cost of failure. When regulatory systems break down or become unbalanced, the same processes that should support regeneration can drive fibrosis, persistent inflammation, or immune escape. In transplanted tissue, the tolerance problem is even sharper: the immune system must avoid rejecting the graft while still defending against infection and preserving host defense.
That tension makes the topic relevant to several linked clinical domains. Fibrotic remodeling can trap tissues in a non-healing state. Chronic inflammation can keep wound-healing programs switched on long after the original injury has resolved. Autoimmune activation can turn a repair response against self-tissue. In cancer, immune tolerance mechanisms may be repurposed by tumors to avoid immune clearance. Each of those outcomes reflects the same underlying issue: the immune system’s repair functions are not separate from its suppressive functions; they are interwoven.
The Research Topic asks contributors to clarify where the boundary lies between productive regulation and harmful immune silence. That question is especially important for therapies that seek to accelerate regeneration. A treatment that quiets immunity too aggressively may improve short-term repair metrics while opening the door to infection, graft injury, or malignant escape.
The call reaches from basic biology to clinical studies
Submissions are welcomed across basic, translational, and clinical research, with article types including Original Research, Review, Mini Review, and Perspective. The topic also lists broader formats such as Case Report, Clinical Trial, Methods, and Systematic Review, reflecting an interest in work that can bridge mechanistic insight and bedside application.
The preferred themes are tightly defined. They include the role of myeloid-derived suppressor cells and tolerogenic myeloid populations in regeneration and repair; regulatory T cells and other lymphocyte subsets in tissue healing; interactions between natural killer cells, innate lymphoid cells, and regulatory myeloid cells; immune tolerance in liver regeneration, cardiovascular repair, and other organ-specific contexts; transplantation and regenerative medicine, including graft acceptance; and the transition from regulated repair to fibrosis, chronic inflammation, or autoimmunity. High-dimensional profiling approaches also figure prominently, especially global gene expression profiling and high-dimensional cytometry used to map immune states during injury and recovery.
Those methods matter because repair is dynamic. Static snapshots often miss the point. A tissue may look inflamed at one time point, suppressive at another, and fibrotic by the end of the course. Deep profiling offers a way to capture those shifts as immune populations move from clearance to suppression to remodeling.
The deadline signals a long runway for mechanistic and translational work
The Research Topic is currently accepting manuscripts, and the submission deadline is 2 May 2027. That long window suggests the editors want a broad and durable collection rather than a narrow burst of one-off observations. The subject area is housed in Frontiers in Immunology, within the section on Immunological Tolerance and Regulation, which fits the topic’s focus on how the immune system maintains control during tissue recovery.
The editors listed for the topic bring together expertise from cancer biology, immunology, and clinical research, while a topic coordinator from Vanderbilt University Medical Center supports the submission process. The journal also makes clear that accepted manuscripts are subject to rigorous peer review and may incur publishing fees, depending on who bears the cost at publication.
What gives this call its clinical weight is not novelty for its own sake, but the practical problem it tries to solve. Regeneration without immune homeostasis is unstable. Immune tolerance without adequate defense is unsafe. The field now needs studies that explain how to preserve both at once, across tissues, across disease states, and across the transition from injury to repair to scar.