September 25, 2014

A path to sarcoidosis treatment

Vanderbilt investigators identify a new therapeutic target for the inflammatory lung disease sarcoidosis.

by Yan Su

Sarcoidosis is an inflammatory disease often found in the lungs, and the incidence has been increasing in recent years. However, no effective treatment for sarcoidosis has been identified.

In recent studies, patients with chronic sarcoidosis have been found to have dysfunctional CD4+ T-cells, a type of immune cell. Immunoregulation, including up-regulation of the programmed death-1 (PD-1) receptor, may be important for CD4+ T-cell proliferation.

In the Sept. 1 issue of the American Journal of Respiratory and Critical Care Medicine, Wonder Drake, M.D., and colleagues used microarray analysis, immunohistochemistry, and flow cytometry studies to understand the relationship between the PD-1 pathway and CD4+ T-cell function. They found increased PD-1 expression in peripheral and local CD4+ T-cells, as well as in sarcoidosis granulomas – abnormal collections of inflammatory cells – in sarcoidosis patients.

The functional significance of PD-1 up-regulation is noted by blocking the PD-1 pathway, which restored CD4+ T-cell proliferative capacity. Targeting this pathway may help restore local and systemic immunity in people with pulmonary sarcoidosis.

This research was supported by grants from the National Institutes of Health (HL103179, HL069765, HL112694, RR024975, HL112707, CA152662), The Mona Eliassen Foundation and The Pierce Foundation.

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