From intestinal immune niches to systemic inflammation: programming cellular plasticity and immune redistribution across organs

Abstract

Immune-mediated inflammatory diseases have traditionally been investigated within organ-specific frameworks. Although increasing evidence has revealed extensive communication along individual gut-organ axes, these interactions are often described through separate mechanisms, including microbial dysbiosis, barrier disruption, soluble mediators, and immune-cell redistribution. A central challenge remains to determine how intestinal immune states are established and how they are translated into organ-specific inflammatory responses. In this review, we propose that the intestine functions as a dynamic immune programming niche for mobile immunity, where microbial, epithelial, and stromal signals collectively shape immune-cell states before their systemic dissemination. Through this niche-dependent education, immune cells acquire distinct phenotypic and migratory programs, while retaining sufficient plasticity to be further reconfigured within peripheral tissues. By integrating evidence across the gut-liver, gut-joint, gut-skin, gut-brain, and other organ axes, we establish a framework in which intestinal immune niches are followed by systemic trafficking, tissue-specific recruitment, and local functional reprogramming. This perspective shifts the focus of gut-organ communication from isolated organ interactions toward a directional process involving immune-cell generation, trafficking, and tissue-specific adaptation. This perspective reframes gut-organ communication as gut-driven immune redistribution rather than isolated organ-axis interactions, highlights intestinal immune programming and immune-cell trafficking as potential targets for systemic immune intervention.