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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’.

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.

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.

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