Abstract:
:Toll-interacting protein (TOLLIP) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole trafficking. The distinct functions of this protein have been linked to innate immune responses and lung epithelial cell apoptosis. TOLLIP genetic variants have been associated with a variety of chronic lung diseases including idiopathic pulmonary fibrosis, asthma, primary graft dysfunction following lung transplantation, and with infections such as tuberculosis, Legionella pneumonia, and respiratory viruses. TOLLIP exists in a delicate homeostatic balance, with both positive and negative effects on the trajectory of pulmonary diseases. This translational review summarizes the genetic and molecular associations that link TOLLIP to the development and progression of non-infectious and infectious pulmonary diseases. We highlight current limitations of in vitro and in vivo models in assessing the role of TOLLIP in these conditions, and we describe future approaches that will enable a more nuanced exploration of the role of TOLLIP in pulmonary conditions. There has been a surge in recent research evaluating the role of of this protein in human diseases, but critical mechanistic pathways require further exploration. By understanding its biologic functions in disease-specific contexts, we will be able to determine whether TOLLIP can be therapeutically modulated to treat pulmonary diseases.
journal_name
Am J Respir Cell Mol Biolauthors
Li X,Goobie GC,Gregory AD,Kass DJ,Zhang Ydoi
10.1165/rcmb.2020-0470TRsubject
Has Abstractpub_date
2020-11-24 00:00:00eissn
1044-1549issn
1535-4989pub_type
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