Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.
TOLLIP (Toll-interacting protein) 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, and primary graft dysfunction after 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 noninfectious 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 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.
['Li|Xiaoyun|X|0000-0003-0000-9171', 'Goobie|Gillian C|GC|0000-0001-7982-5635', 'Gregory|Alyssa D|AD|0000-0002-0392-7202', 'Kass|Daniel J|DJ|0000-0001-6597-7830', 'Zhang|Yingze|Y|0000-0001-6947-2901']
D000818:Animals D001249:Asthma D016207:Cytokines D004195:Disease Models, Animal D005786:Gene Expression Regulation D006084:Graft Rejection D006801:Humans D054990:Idiopathic Pulmonary Fibrosis D007113:Immunity, Innate D047908:Intracellular Signaling Peptides and Proteins D007877:Legionnaires' Disease D016040:Lung Transplantation D051379:Mice D035683:MicroRNAs D010253:Respirovirus Infections D015398:Signal Transduction D014397:Tuberculosis, Pulmonary
lung diseases TOLLIP protein biomarkers communicable diseases genetic research