Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy.

Nature Genetics
Daniel KotlarzChristoph Klein

Abstract

Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis1,2. Following its discovery 3 , enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties4,5, pro- and anti-inflammatory effects 6 , or pro- and anti-fibrinogenic characteristics 7 . Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1-LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans.

References

May 4, 2000·The New England Journal of Medicine·G C BlobeH F Lodish
Aug 24, 2001·The Journal of Clinical Investigation·G MonteleoneT T MacDonald
Mar 23, 2006·Annual Review of Immunology·Ming O LiRichard A Flavell
Nov 3, 2006·The Journal of Clinical Investigation·Ina TesseurTony Wyss-Coray
Aug 12, 2008·Cell·Ming O Li, Richard A Flavell
Mar 18, 2009·Developmental Cell·Mary Y Wu, Caroline S Hill
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 23, 2009·Biochimica Et Biophysica Acta·Dirk PohlersGunter Wolf
Nov 6, 2009·The New England Journal of Medicine·Erik-Oliver GlockerChristoph Klein
Jun 17, 2011·Nature·Minlong ShiTimothy A Springer
Feb 27, 2013·The Journal of Experimental Medicine·Daniel KotlarzChristoph Klein
Feb 11, 2014·Journal of the National Cancer Institute·Daniel R PrincipePaul J Grippo
Mar 19, 2015·The New England Journal of Medicine·Giovanni MonteleoneFrancesco Pallone
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium

❮ Previous
Next ❯

Citations

Jun 20, 2018·Current Opinion in Rheumatology·Florence A Aeschlimann, Ronald M Laxer
Jan 12, 2019·Immunological Medicine·Hirokazu Kanegane
Oct 5, 2019·Clinical and Translational Gastroenterology·Mona Dixon GundersenRuth Hracky Paulssen
Feb 28, 2020·Nature·Daniel B Graham, Ramnik J Xavier
Feb 27, 2020·Acta Neuropathologica·Colin SmithYanick J Crow
Mar 4, 2020·Annual Review of Immunology·Joshua D Milner
Jun 13, 2020·Human Vaccines & Immunotherapeutics·Anissa A WidjajaStuart A Cook
Oct 10, 2018·Current Opinion in Allergy and Clinical Immunology·Kathleen E SullivanJudith R Kelsen
Oct 10, 2018·Current Opinion in Allergy and Clinical Immunology·Vritika Batura, Aleixo M Muise
Mar 11, 2020·Journal of Medical Genetics·Priyam JaniJanice S Lee
Mar 9, 2019·The Journal of Experimental Medicine·Thomas D ArnoldDean Sheppard
May 23, 2019·Inflammatory Bowel Diseases·Thomas MaggDaniel Kotlarz
Sep 4, 2019·Journal of Clinical Immunology·Peter GeorgievTalal A Chatila
Mar 8, 2019·Science Translational Medicine·Gerard E KaikoThaddeus S Stappenbeck
Aug 18, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Brian H Kim, Steven W Levison
Mar 25, 2019·Journal of Clinical Immunology·David IlligDaniel Kotlarz
Jun 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Morten T VenøDavid C Henshall
Sep 22, 2020·EMBO Molecular Medicine·Mark SweeneyStuart A Cook
Jan 6, 2021·Clinical Science·Jitske van den BulkPeter Ten Dijke
Mar 9, 2021·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Demet Teker DuztasOdul Egritas Gurkan
Apr 17, 2021·Mucosal Immunology·Fabienne Charbit-HenrionNadine Cerf-Bensussan
May 4, 2021·Gastroenterology·Nancy R GoughLopa Mishra
Aug 3, 2021·Frontiers in Pharmacology·Linshan DuanGuoyan Liu
Jul 21, 2021·Disease Models & Mechanisms·Woutje M BerdowskiTjakko J van Ham
Mar 18, 2020·Genes & Diseases·Johnson NameirakpamDeepti Suri
Oct 21, 2021·Current Opinion in Pediatrics·Yesim DemirdagJoyce E Yu
Jan 13, 2022·Clinical Reviews in Allergy & Immunology·Margaret T RedmondBenjamin T Prince

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISAs
biopsies
antisense oligonucleotides
Exome Sequencing
transfection
PCR
flow cytometry
ELISA
Assay

Software Mentioned

VEP
Prism
FlowJo
GraphPad
PyMol
BWA
Variant Effect Predictor (
Ensembl
CyTOBANK
DNASTAR Lasergene

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Current Opinion in Gastroenterology
Elisa K Boden, Scott B Snapper
International Journal of Biological Sciences
Evangelia Pardali, Peter Ten Dijke
© 2022 Meta ULC. All rights reserved