The human immune response has both a rapid innate component and a slower but more specific adaptive component. The innate immune response involves the action of phagocytic and cytotoxic cells, which rapidly migrate to the site of infection and produce antimicrobial compounds. Innate immunity not only regulates the inflammatory response; it also plays a key role in the activation of adaptive immunity, which involves cells and immune mediators such as T cells, B cells, and antibodies. Thus, a robust innate immune response is critical for fighting infection.
Of course, too much of a good thing is not necessarily good. If the innate immune response becomes activated chronically, this can contribute to the pathogenesis of many different diseases with an inflammatory component. Thus it is critical not only that innate immunity is activated when needed (upon infection) but that this response is also self-limiting and ultimately inactivated when no longer needed.
Dr. Alper's laboratory is focused on understanding the regulation of the innate immune response, particularly as it relates to the basis for inflammatory disease. The signaling pathways involved in the activation of innate immunity have been studied by numerous labs. In contrast, the pathways that terminate this response are much less understood. The Alper laboratory is investigating two signaling mechanisms that terminate persistent inflammation and therefore prevent chronic inflammatory disease: the regulation of alternative splicing in the Toll-like receptor (TLR) signaling pathway, and the subcellular trafficking of TLR signaling pathway components. Understanding how the maintenance of TLR signaling is regulated offers the potential to devise ways to ensure that inflammation is limited—activated to fight infection but terminated to prevent diseases with an inflammatory component such as COPD, atherosclerosis, and cancer.
De Arras L, Yang IV, Lackford B, Riches DWH, Prekeris R, Freedman JH, Schwartz DA and Alper S. Spatiotemporal inhibition of innate immunity signaling by the Tbc1d23 RAB-GAP. J. Immunol. 188: 2905-13 (2012).
De Arras, L, Seng, A, Lackford, B, Keikhaee, MR, Bowerman, B, Freedman, JH, Schwartz, DA and Alper, S. An evolutionarily conserved innate immunity protein interaction network. J. Biol. Chem. 288: 1967-1978 (2013).