Editors' ChoiceImmunology

Trafficking from bedside to bench

Sci. Signal.  28 Jul 2015:
Vol. 8, Issue 387, pp. ec209
DOI: 10.1126/scisignal.aad0885

Typically in translational research, a discovery in cell or molecular biology is later exploited to improve patient care. Occasionally, information flows in the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of a protein called LRBA responded dramatically to the drug abatacept (see the Perspective by Sansom). Abatacept contains a segment of a potent inhibitory immune receptor, CTLA4. Experiments prompted by this observation revealed the relationship between the two proteins: LRBA controls the intracellular trafficking and degradation of CTLA4. This information may further improve patient care, because other clinically approved drugs have the desired mechanism of action with potentially fewer side effects.

B. Lo, K. Zhang, W. Lu, L. Zheng, Q. Zhang, C. Kanellopoulou, Y. Zhang, Z. Liu, J. M. Fritz, R. Marsh, A. Husami, D. Kissell, S. Nortman, V. Chaturvedi, H. Haines, L. R. Young, J. Mo, A. H. Filipovich, J. J. Bleesing, P. Mustillo, M. Stephens, C. M. Rueda, C. A. Chougnet, K. Hoebe, J. McElwee, J. D. Hughes, E. Karakoc-Aydiner, H. F. Matthews, S. Price, H. C. Su, V. K. Rao, M. J. Lenardo, M. B. Jordan, Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 349, 436–440 (2015). [Abstract] [Full Text]

D. M. Sansom, Moving CTLA-4 from the trash to recycling. Science 349, 377–378 (2015). [Abstract] [Full Text]