Immune cells such as lymphocytes constantly traverse throughout the body in search of infection. Two reports in the September issue of Nature Immunology suggest exit of immune cells from peripheral tissues does not passively occur but requires the expression of a specialized receptor called CCR7.
Earlier work revealed lymphocytes exit the bloodstream to percolate through the tissues, such as the lung or skin, and then return to the bloodstream via an indirect route. These traveling cells re-enter the blood through lymphatic vessels that channel cells and excess fluids towards regional lymph nodes. Cells can then exit lymph nodes to re-enter blood. This process was thought to occur passively by hydrodynamic pressure differences between tissues and lymph fluid.
Now, Butcher and colleagues show lymphocyte tissue exit is not random. They noticed increased numbers of T lymphocytes that expressed the chemokine receptor CCR7 in lymph fluid, whereas cells that did not express CCR7 were retained in the tissues. This finding suggested some selective process was at work. Lymphocytes from CCR7 mutant mice failed to enter lymphatic vessels and instead accumulated in tissues. Independently, Luster and colleagues also found CCR7 was required for lymphocyte exit from lungs in a mouse model of asthma. Accordingly, CCR7 is the ticket for lymphocytes making their way out of tissues. Immune modulators that communicate through CCR7 could therefore potentially be used to alter the course of local inflammatory reactions where lymphocytes accumulate.
Andrew D Luster (Harvard Medical School and Massachusetts General Hospital, Charlestown, MA, USA)
Eugene C Butcher (Stanford University School of Medicine, Stanford, CA, USA)
Additional comment on papers:
Sergio A Lira (Mt. Sinai School of Medicine, New York, NY, USA)
Abstracts available online: Abstract 1, and Abstract 2.
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza