Mechanoimmunology: past, present, and future perspectives

The immune system relies on intricate molecular interactions and cellular signaling to discriminate between self and non-self, mount appropriate responses to pathogens and cancer, and maintain tissue homeostasis to avoid autoimmune diseases. Evidence increasingly supports the critical role of mechanical forces in regulating immune cell function and differentiation through immunoreceptor interactions with immobilized ligands, leading to the emerging interdisciplinary field of mechanoimmunology. This review delves into the historical development and recent advances of the field. We highlight the key concepts and questions in understanding how immune cells perceive and respond to mechanical cues, with a focus on the critical role of catch bonds in immunoreceptor-mediated mechanotransduction and explore their immunotherapeutic applications. Furthermore, we explore the profound implications of mechanoimmunology for understanding major immunological problems and its potential applications in advanced immunotherapies and regenerative medicine.