In the Shadow of Fibrosis: Innate Immune Suppression Mediated by Transforming Growth Factor-β.
Transforming growth factor-β (TGFB) regulates cell proliferation, differentiation, apoptosis, and matrix homeostasis and is intimately involved in fibrosis. TGFB expression is increased in fibrotic lung diseases, such as idiopathic pulmonary fibrosis, and in chronic inflammatory conditions, such as chronic obstructive pulmonary disease and asthma. In addition to exhibiting profibrotic activities, the protein exhibits profound immune-suppressive actions involving both innate and adaptive responses, but often this aspect of TGFB biology is overlooked. Recent investigations have demonstrated that TGFB causes wide-ranging immune suppression, including blunting of pivotal early innate IFN responses. These activities permit severe virus infections, often followed by secondary bacterial infections, which may last longer, with augmented inflammation, scarring, fibrosis, and loss of lung function. Strategies to oppose TGFB actions or to enhance IFN responses may help ameliorate the detrimental consequences of infection in patients with diseases characterized by TGFB overexpression, inflammation, and fibrosis.
1 Monash Lung and Sleep, Monash Medical Centre, Melbourne, Victoria, Australia.|2 Centre for Innate Immunity and Infectious Diseases and.|3 Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia; and.
Belinda J
0000-0002-4035-8141
BJ
Thomas
1 Monash Lung and Sleep, Monash Medical Centre, Melbourne, Victoria, Australia.|2 Centre for Innate Immunity and Infectious Diseases and.|3 Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia; and.
Keiko
K
Kan-O
4 Centre of Reproductive Health, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.|3 Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia; and.
Kate L
0000-0002-5750-8046
KL
Loveland
5 Division of Biology and Medicine, Brown University, Providence, Rhode Island.
Jack A
0000-0002-3124-8557
JA
Elias
1 Monash Lung and Sleep, Monash Medical Centre, Melbourne, Victoria, Australia.|2 Centre for Innate Immunity and Infectious Diseases and.|3 Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia; and.
Philip G
PG
Bardin
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008954:Models, Biological; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta
idiopathic pulmonary fibrosis; immunity; lung disease; transforming growth factor-β; virus infection