Editors' ChoiceImmunology

Lowering the bar for autoimmunity

Sci. Signal.  16 Jun 2015:
Vol. 8, Issue 381, pp. ec159
DOI: 10.1126/scisignal.aac7869

In patients with autoimmune diseases, such as multiple sclerosis, immune cells attack the tissues that they are supposed to protect. However, it remains unclear why these self-targeted cells become activated in some individuals and not in others. Housley et al. showed that at least some multiple sclerosis patients have genetic variants that result in increased NF-κB signaling after stimulation with the cytokine TNFα. These variants, in effect, lower the activation threshold of CD4+ T cells, making them more responsive to inflammation and thus more likely to contribute to autoimmunity. Patients with these variants may be good candidates for therapies that block either NF-κB signaling or inflammatory cytokines.

W. J. Housley, S. D. Fernandez, K. Vera, S. R. Murikinati, J. Grutzendler, N. Cuerdon, L. Glick, P. L. De Jager, M. Mitrovic, C. Cotsapas, D. A. Hafler, Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli. Sci. Transl. Med. 7, 291ra93 (2015). [Abstract]