Characterizing Function & Development of Meningeal & Choroid Plexus Dendritic Cells in the Mouse Brain

Kang Liu, Ph.D.

Columbia University

Funded in June, 2010: $200000 for 3 years
LAY SUMMARY .

LAY SUMMARY

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Learning how innate immune cells directly help shape the brain’s responses to infections

This study will help define the multiple roles of immune dendritic cells in shaping the central nervous system’s (CNS) immune responses to infections, and also in maintaining CNS health.

Dendritic cells are innate immune cells, the body’s first line of defense. They recognize invaders and mount a rapid, generalized short response. They also summon specific “adaptive” immune T cells, the body’s second line of defense, to mount a sustained highly targeted attack against invaders. Additionally, evidence suggests that adaptive immunity may also confer neuroprotection. Studies of cancer patients who experience cognitive problems while undergoing immunosuppressive chemotherapy improve cognitively once chemotherapy is completed and their immune systems are no longer suppressed. Now researchers have found that some dendritic cells and adaptive T cells in the healthy (“steady state”) reside in structures near brain tissues. They are found the in the choroid plexus—a membrane in the fluid spaces of the brain that secretes cerebrospinal fluid—and in the meninges—the membranes that surround and protect the CNS, (brain and spinal cord). The meninges and choroid plexus also serve as gates for T cells to enter the brain.

The investigators hypothesize that dendritic cells in these gateway structures contribute to shaping immune responses in the CNS by directly conditioning T cells at these sites of entry into the CNS.   They will study dendritic cells’:1) origin and turnover in the steady state (health); 2) their development; and 3) how they condition T cells to recognize an invader. They then will study how T cells may regulate “microglia,” the only immune cells that reside in the brain and mount an inflammatory response to brain tissue damage.

Significance: Greater understanding of how dendritic cells condition T cells residing in these gateway structures to the CNS can potentially lead to new strategies for strengthening immune responses to brain infections.