Evolution of L-arginine: From metabolic pathways to immune modulation

L-Arginine metabolism represents a cornerstone in the field of immunometabolism, bridging fundamental biochemical processes with sophisticated immune functions. Long appreciated for its role in protein synthesis and as a precursor to nitric oxide, L-Arginine has become recognized as a crucial modulator of immune responses—especially within T cell biology. Contemporary research has uncovered how L-Arginine availability can dictate T cell fate decisions, influence metabolic reprogramming, and impact the transition between activation, memory, and exhaustion states. Despite decades of study, the intricate relationship between L-Arginine metabolism and immune function continues to present unresolved questions regarding the spatial and temporal regulation within diverse immunological contexts. While recent advances using high-resolution omics and genetic manipulation are enhancing our understanding, the precise mechanisms and broader implications for immune defense and pathology remain a topic of active investigation.This Research Topic aims to delineate the evolution of knowledge regarding L-Arginine’s dual identity as both a metabolic substrate and an immunoregulatory signal, with a concentrated focus on T lymphocyte function. The primary objectives are to synthesize historical insights with current findings, highlight unresolved mechanistic questions, and encourage innovative strategies for investigating L-Arginine dynamics in the immune system. Contributors are invited to address how L-Arginine shapes antigen presentation, TCR signaling, effector differentiation, and to explore the pathways that mediate its impact on immune cell homeostasis and disease processes. Ultimately, this topic aspires to illuminate actionable pathways for metabolic intervention and enhancement of T cell responses.The scope of this Research Topic encompasses mechanistic, translational, and interdisciplinary approaches to L-Arginine metabolism in T cell-mediated immunity, with a particular emphasis on clarifying functional relationships and therapeutic potential. Submissions are welcomed that cover molecular, metabolic, structural, and comparative aspects, but should not extend into broader amino acid metabolism unless directly relevant to L-Arginine’s specific actions in T cell biology. To facilitate comprehensive coverage, themes of interest include, but are not limited to:-Regulatory networks controlling L-Arginine availability and catabolism in immune cells-The impact of L-Arginine on T cell receptor signaling and downstream pathways-L-Arginine’s influence on T cell differentiation, exhaustion, and memory formation-Interactions between L-Arginine metabolism and immunoregulatory enzymes (e.g., iNOS, arginases, mTOR, AMPK)-Emerging methodologies for studying immunometabolic dynamics (e.g., metabolomics, CRISPR-Cas, single-cell analysis)-Comparative analyses across disease models and species-Translational potential for targeting L-Arginine pathways in immunotherapyWe invite reviews, original research articles, methodological reports, and interdisciplinary studies that provide conceptual advances or translational insights into L-Arginine metabolism in the immune context. The topic editors declare no conflict of interest Topic editors: Jochen Mattner, Guangju Zhai Source: https://www.frontiersin.org/research-topics/76062/evolution-of-l-arginine-from-metabolic-pathways-to-immune-modulation