Regulators of immune cell ‘walking’

Molecular regulators of immune cell ‘walking’ through tissues are identified in a report published online this week in Nature Immunology.

Immune cells travel in the blood and can enter tissues as a result of signals released during infection or inflammation. Upon exiting the bloodstream, cells morph from a round shape into an elongated form that can move in an inchworm or crawling manner into the tissue. Such directional movement in the infected tissue requires a precise coordination of ‘stepping forward’ and ‘release’.

Andy Luster and colleagues identify several new regulatory molecules called synatotagmins (SYT) that are necessary for the cell ‘foot’ to step forward and release such that migration occurs. These molecules are sensitive to calcium fluxes that occur inside migrating cells that respond to chemical ‘scents’ known as chemoattractants. Cells lacking either SYT7 or a related synatotagmin-like molecule SYTL5 fail to move and behave as if the trailing foot is stuck and unable to release. Cells lacking SYT2 move faster and display defects in stopping.

In a gout disease model mice lacking SYT7 recruit fewer inflammatory cells into the affected tissue. The scientists suggest these defects may be related to a human immunodeficiency disease called Chediak-Higashi syndrome where immune cells display defective migration.