Myelin is targeted in MS by both innate and adaptive immune cells. We have observed a role for a vanilloid-type member of the Transient Receptor Potential (TRP) channel family, TRPV4 in EAE. In collaboration with Hongzhen Hu from the Center for the Study of Itch, we have observed in preliminary studies the expression of TRPV4 by immune cells. We are presently testing the requirement for innate immune cell expression of TRPV4 during neuro-inflammation using in vivo genetic manipulation of TRPV4. Additionally, we are pursuing studies using human specimens to explore whether TRPV4 is involved in the development of inflammatory demyelinating MS plaques.