A mechano-immunological method for estimating the evolutionary stress in lymph nodes during immune response

During the immune responses of lymph nodes (LNs), the interior stress undergoes significant nonlinear dynamic evolution, which critically influences immune cell activation and tissue remodeling. Stress analysis is essential for revealing the role of mechanical stresses within LNs, including the mechanosensitivity of T-cell activation. However, previous approaches usually rely on direct in situ measurement, which is technically demanding and experimentally difficult. This highlights the need for a more accessible and efficient method for determining the interior stress in LNs. In this paper, we propose a facile method to estimate the stress in LNs based on our recently established mechano-immunological theory. Explicit formulations are derived to describe the dynamic evolutions of deformation and interior stress in a LN during immune response. Thereby, one can rapidly predict the interior stress from the easily measurable LN volume changes, without the need for in situ mechanical tests. Validation against experimental data from multiple independent studies demonstrates the robustness and generalizability of this method across a wide range of immunological conditions, including variations in mouse strains, antigen-adjuvant types, and dosages. This work provides a practical tool for investigating stress-mediated immune regulation and offers potential for clinical applications in diagnosing and monitoring LN-associated pathologies.