A mechano-immunological framework for lymph node remodeling during inflammation and homeostasis

During the immune response, lymph nodes (LNs) undergo significant coupled evolutions in their geometric structures, cellular compositions, and mechanical properties. The efficiency of the immune response (IR) is governed by the interplay between internal cellular activity and mechanical deformation throughout the inflammation–homeostasis process. While mechanical forces are known to play a crucial role in LN remodeling, the underlying mechanisms of mechano-immunology synergy within LNs remain poorly understood. In this paper, we propose a mechano-immunology theory that conceptualizes LNs as integrated, dynamically evolving structures during IR and establish a mechano-immunological landscape to quantify distinct LN states. This framework introduces a novel paradigm for evaluating IR efficiency based on metrics derived from mechano-chemo-biological mechanisms. We identify the range of mechanical properties that optimize IR efficiency and propose that immune exhaustion in tumor-draining LNs arises from mechanical damage, leading to an immune anergic state. Using the proposed mechano-immunological methodology, we demonstrate that this anergic state can be mitigated by modulating collective immune cell migration to align with the optimal IR efficiency range, thereby offering potential therapeutic strategies to enhance IR efficiency.