Tissue tolerance: a distinct concept to control acute GVHD severity

Area of Science:

• Immunology
• Transplantation Biology
• Tissue Engineering

Background:

• Acute graft-versus-host disease (GVHD) is a severe complication of allogeneic stem cell transplantation, primarily attributed to pathological immune responses.
• Current management strategies for GVHD predominantly focus on modulating immune cells to induce immune tolerance.
• The contribution of tissue-intrinsic factors to GVHD severity has been largely overlooked.

Purpose of the Study:

• To introduce and define the concept of "tissue tolerance" in the context of alloimmune diseases.
• To explore tissue-specific programs that influence resilience, repair, and regeneration in GVHD.
• To propose "tissue tolerance" as a novel therapeutic avenue for mitigating GVHD severity.

Main Methods:

• Literature review and conceptual framework development.
• Analysis of existing data on tissue responses in alloimmune settings.
• Comparative analysis with plant immune responses to disease.

Main Results:

• Tissue-intrinsic factors play a significant, yet underappreciated, role in modulating GVHD severity.
• The concept of "tissue tolerance" encompasses mechanisms of target tissue resilience, repair, and regeneration.
• Targeting tissue tolerance may mitigate GVHD without compromising necessary immune cell function.

Conclusions:

• "Tissue tolerance" represents a paradigm shift in understanding and managing GVHD.
• Harnessing tissue-intrinsic repair and resilience mechanisms offers a promising strategy for GVHD treatment.
• Future research should focus on identifying and manipulating these tissue-specific programs to improve transplant outcomes.