Neuroanatomy of lymphoid organs: Lessons learned from whole-tissue imaging studies

Decades of extensive research have documented the presence of neural innervations of sensory, sympathetic, or parasympathetic origin in primary and secondary lymphoid organs. Such neural inputs can release neurotransmitters and neuropeptides to directly modulate the functions of various immune cells, which represents one of the essential aspects of the body's neuroimmune network. Notably, recent studies empowered by state-of-the-art imaging techniques have comprehensively assessed neural distribution patterns in BM, thymus, spleen, and LNs of rodents and humans, helping clarify several controversies lingering in the field. In addition, it has become evident that neural innervations in lymphoid organs are not static but undergo alterations in pathophysiological contexts. This review aims to update the current information on the neuroanatomy of lymphoid organs obtained through whole-tissue 3D imaging and genetic approaches, focusing on anatomical features that may designate the functional modulation of immune responses. Moreover, we discuss several critical questions that call for future research, which will advance our in-depth understanding of the importance and complexity of neural control of lymphoid organs.

Automated summary

Decades of research have demonstrated the presence of neural innervations in primary and secondary lymphoid organs, which release neurotransmitters and neuropeptides to directly modulate immune cells. Recent studies using advanced imaging techniques have clarified the neural distribution patterns in rodents and humans. It has been found that neural innervations in lymphoid organs are not static and undergo changes in pathophysiological conditions. This review aims to update the current knowledge on the neuroanatomy of lymphoid organs, focusing on anatomical features that can modulate immune responses, and identifies important questions for future research.