Understanding Kidney Disease through the Nervous and Immune Systems

  We investigate how the nervous system regulates immune responses and how these interactions influence kidney injury and tissue repair.Our research focuses on neuro–immune–organ interactions originating from the vagus nerve and sympathetic nervous system. By combining animal models, neural stimulation, molecular biology, optogenetics, single-cell analysis, and other advanced approaches, we aim to uncover the mechanisms underlying these complex interactions.Why can manipulating neural activity protect the kidney? By addressing this question step by step, we seek to translate discoveries from basic science into new therapeutic strategies for kidney disease.

Cholinergic Anti-inflammatory Pathway

  The nervous and immune systems were once regarded as largely independent systems. It is now clear, however, that neural signals can alter immune-cell function and thereby regulate inflammation and organ injury. One of the best-known examples is the cholinergic anti-inflammatory pathway (CAP), illustrated in the figure above, in which vagus nerve–initiated signals suppress excessive inflammatory responses. Acetylcholine generated through this pathway acts on immune cells, including macrophages, to modulate inflammation.
  We have long been interested in this pathway and have demonstrated that vagus nerve stimulation can attenuate acute kidney injury (AKI), and that immune cells in the spleen play an important role in this renoprotective effect. We have subsequently expanded our research to define the neural–immune network connecting the central nervous system, peripheral nerves, spleen, immune cells, and kidney, as well as to investigate novel renoprotective mechanisms mediated by the sympathetic nervous system. In particular, we have reported a number of pioneering findings on neuroimmune interactions in AKI.
  Neuroimmune interactions, however, represent a highly complex system involving the brain, peripheral nerves, immune cells, the kidney, and other organs. Which nerves are activated? Which cells receive these signals? And how do these signals ultimately protect the kidney? Many aspects of this network remain unknown.To unravel these mechanisms, we combine multiple approaches, including selective manipulation of neural activity, analysis of cellular responses at single-cell resolution, and the development of novel methods for neural stimulation. By integrating neuroscience, immunology, and nephrology, we aim to translate mechanistic discoveries into new therapeutic approaches.

Optogenetics | Controlling Neural Activity with Light

  The nervous system consists of many different types of neurons, each with distinct functions. Optogenetics enables us to selectively stimulate or control specific populations of neurons using light.We use this technology to investigate which neural pathways protect the kidney and how neural signals are transmitted to the immune system and the kidney. Whereas conventional electrical stimulation can activate multiple types of nerve fibers simultaneously, optogenetics allows specific neural populations to be manipulated selectively, making it a powerful tool for dissecting complex neuroimmune networks.
  The photograph on the bottom shows wireless optogenetic stimulation of the cervical vagus nerve in a freely moving mouse. By manipulating neural activity while preserving physiological behavior as much as possible, we can investigate how neural stimulation influences inflammation and kidney injury.

Single-Cell Analysis | Understanding Biology One Cell at a Time

  The kidney and immune organs are composed of many different cell types. Single-cell analysis enables us to move beyond averaged measurements of whole tissues and examine, cell by cell, which cells respond to neural stimulation and what molecular and transcriptional changes occur within those cells.
  We were among the pioneers in introducing single-cell analysis into kidney research in Japan (Figure below adapted from J Am Soc Nephrol 2021) and have accumulated extensive technical expertise and experience in this field. We now apply these approaches to the study of neuro–immune–kidney interactions, identifying cells that respond to neural stimulation and defining the changes that occur within them to uncover previously unrecognized mechanisms of kidney protection.
  Building on this expertise, we also collaborate with research laboratories in Japan and abroad, contributing to single-cell experiments and data analysis across a wide range of research projects and disease areas. Through these collaborations, we continue to expand both the applications and the possibilities of single-cell analysis.

Ultrasound Neuromodulation | Stimulating the Nervous System from Outside the Body

  Ultrasound neuromodulation is an emerging technology that uses externally applied ultrasound to alter neural activity. Unlike conventional approaches that require electrodes to be implanted around nerves, ultrasound has the potential to modulate neural pathways noninvasively, making it an attractive platform for the development of new therapeutic strategies.
  We have demonstrated that abdominal ultrasound stimulation activates vagal afferent pathways (PNAS 2026). We are now investigating how this stimulation engages neuroimmune circuits to suppress inflammation and protect organs from injury.
  Our ultimate goal is to develop a new therapeutic concept: treating inflammation and kidney injury by stimulating neural pathways from outside the body. Our research spans the entire process, from elucidating the underlying mechanisms to developing technologies with the potential for future clinical translation.

Neuroimmune Interactions across Organs

  Neuroimmune interactions are not unique to the kidney. We are expanding our research across organ systems to understand how interactions between the nervous and immune systems contribute to inflammation and tissue injury in different organs.
  Our current research includes bronchial asthma (Front Immunol, 2026), radiation-induced pharyngeal and vocal fold injury (Lab Anim Res, 2024; Laryngoscope, 2025), interstitial cystitis, atherosclerosis (BBRC, 2022), and hypertension (BBRC, 2024; J Physiol Sci, 2024). In each of these conditions, we investigate the role of neuroimmune interactions and explore the potential of modulating these pathways as novel therapeutic strategies.
  By extending the neural manipulation and immune-analysis approaches developed through our kidney research to other organ systems, we aim to uncover fundamental principles of neuroimmune regulation that are shared across organs.

Research tools & technologies

  Our laboratory provides an integrated research environment that supports experiments from molecular biology and cell-based studies to functional analyses in mouse models. A key strength of our laboratory is the ability to investigate biological questions across multiple levels—from molecules and cells to tissues and whole animals.Our laboratory is equipped with a broad range of molecular and cellular biology platforms, including real-time PCR systems, electroporation and cell culture systems, hypoxia culture equipment, and multimode plate readers. Major instruments include an Attune NxT Flow Cytometer (3 lasers, 11 colors), MACS / autoMACS systems, Wes capillary Western blot system, KEYENCE BZ-X1000, EVOS M5000, Nikon ECLIPSE Ci-L, and 10x Genomics Chromium iX, enabling immune-cell profiling, protein analysis, imaging, and single-cell analysis.
  For in vivo studies, our laboratory owns and operates a dedicated set of equipment housed in the animal research facility, including systems for noninvasive and invasive blood pressure measurement, telemetry, blood-flow monitoring, metabolic cage studies, blood gas analysis, and lactate measurement. We also maintain trinocular stereomicroscopes, optogenetic laser and control systems, ultrasound stimulation devices, and neural activity recording systems. These platforms allow us to manipulate and monitor neural activity while assessing cardiovascular, renal, immune, and organ-level responses in vivo.
Together, these capabilities allow us to carry out integrated studies from mechanistic discovery to functional validation in vivo.We actively collaborate with research groups in Japan and abroad and welcome collaborative projects that can benefit from our expertise and infrastructure in single-cell analysis, immune-cell profiling, imaging, in vivo physiology, neuromodulation, and neural recording.