Hao Jin, Ph.D.

The Neuro-immune Crosstalk Unit seeks to decode the multidimensional interactions between the immune and nervous systems to understand the multifaceted regulation of host immunity at the whole organismal level.

Immune responses need to be delicately regulated. Imbalance in this regulation can lead to devastating consequences. A less understood but integral dimension of immune regulation is by the nervous system. The intimacy between the immune and nervous systems occurs at many layers, conferring adaptive advantages (e.g., speed, integration and prediction) beyond the autonomous regulation by the isolated immune system. Leveraging emerging neuroscience and immunology tools, we develop and apply integrative multimodal approaches to explore these physiologically rich neuro-immune connections to unravel fundamental principles of neural control of immune responses. Currently, our research centers on the following three areas:

a) Role of body-brain axis in the control of innate immune response

We are examining how the brain monitors and alters peripheral immune responses.  We reasoned that identifying brain neurons activated by immune challenges would open unique windows into the workings of the modulation of immune responses by the brain. Recently, we have identified a neuronal population in the brainstem responsive to peripheral immune insult and showed that activating or silencing this population can bidirectionally alter immune activities. These brainstem neurons receive inputs from peripheral sensory neurons that pervasively innervate immune tissues and barrier sites. Thus, they are poised to surveille and report ongoing immune activities to the brain to drive descending immune modulatory responses. We hypothesize that this body-to-brain axis constitutes a gateway for the control of immune responses by the brain. We therefore combine multiomics, functional imaging and manipulation, and circuit cracking to decipher the cells, circuits and logic for immune sensing and regulation by the bidirectional body-brain ‘highway’.

b) Representation and regulation of distinct types of immune responses by the brain

The immune system has evolved successful immune strategies to counteract invading agents. While a fast-reacting innate response precedes a slow-arising adaptive response, adaptive responses are exquisitely tailored to incoming pathogens (e.g., Th1 or Th2 response against intracellular bacteria and viruses or parasites, respectively). Whether and how the brain customizes its top-down immune modulation according to the immunological needs of different immune responses is an open question. To answer this, we employ an arsenal of neural activity monitoring tools to compare and contrast brain-wide neural responses to categorically distinct immune challenges. This immune-to-brain mapping will then guide the design of targeted manipulation to test the roles of these brain representations and the connected circuits in modulating selective immune responses.

c) Modulation of immune responses by sensory experience and internal states

An important function of brain control of the immune system is to coordinate immune responses with other vital processes. A number of external and internal factors have been shown to influence immune responses via the brain. We are actively investigating how predictive sensory cues (either innate or learned) prime the immune system for a more effective immune response against upcoming infection.

Together, these efforts will help address fundamental questions on the functions and mechanisms of neural regulation of immunity in this emerging frontier of body-brain dialogue. We hope that our basic research on the neural modulation of immune responses would ultimately allow us to innovatively harness the unmatched power of the nervous system to combat various immune-related diseases.