Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

RNA sequencing Ulcerative colitis anti-TNF treatment response intraepithelial compartment spatial transcriptomics

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
05 Jun 2023
Historique:
pubmed: 19 6 2023
medline: 19 6 2023
entrez: 19 6 2023
Statut: epublish

Résumé

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature

Identifiants

pubmed: 37333091
doi: 10.1101/2023.06.02.542863
pmc: PMC10274630
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIDDK NIH HHS
ID : K23 DK111995
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK122532
Pays : United States

Déclaration de conflit d'intérêts

Competing interests: SM reports receiving research grants from Genentech and Takeda; receiving payment for lectures from Takeda, Genentech, Morphic; and receiving consulting fees from Takeda, Morphic, Ferring and Arena Pharmaceuticals. JM reports receiving consulting fees from Janssen Pharmaceuticals. JFC reports receiving research grants from AbbVie, Janssen Pharmaceuticals, Takeda and Bristol Myers Squibb; receiving payment for lectures from AbbVie, and Takeda; receiving consulting fees from AbbVie, Amgen, AnaptysBio, Allergan, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Genentech (Roche), Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Invea, Iterative Scopes, Merck, Landos, Microba Life Science, Novartis, Otsuka Pharmaceutical, Pfizer, Protagonist Therapeutics, Prometheus, Sanofi, Seres, Takeda, Teva, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. JM reports receiving consulting fees from Janssen Pharmaceuticals. RCU has served as an advisory board member or consultant for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Pfizer, Roivant, and Takeda; research support from AbbVie, Boehringer Ingelheim, Eli Lily, and Pfizer. MK has served as a consultant for AbbVie, Pfizer, Bristol Myers Squibb, Fresenius, GoodRx.

Auteurs

Divya Jha (D)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Zainab Al-Taie (Z)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA.

Azra Krek (A)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA.

Shadi Toghi Eshghi (ST)

Biomarker Discovery, OMNI, Genentech Inc. South SanFrancisco, CA, USA.
OMNI Biomarker Development, Genentech Inc. South SanFrancisco, CA, USA.

Aurelie Fantou (A)

Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Thomas Laurent (T)

Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Michael Tankelevich (M)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Xuan Cao (X)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA.

Hadar Meringer (H)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Alexandra E Livanos (AE)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Minami Tokuyama (M)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Francesca Cossarini (F)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Arnaud Bourreille (A)

Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Regis Josien (R)

Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Ruixue Hou (R)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA.

Pablo Canales-Herrerias (P)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ryan C Ungaro (RC)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Maia Kayal (M)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

James Marion (J)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Alexandros D Polydorides (AD)

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Huaibin M Ko (HM)

Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York.

Darwin D'souza (D)

Human Immune Monitoring Core, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Raphael Merand (R)

Human Immune Monitoring Core, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Seunghee Kim-Schulze (S)

Human Immune Monitoring Core, Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jason A Hackney (JA)

Biomarker Discovery, OMNI, Genentech Inc. South SanFrancisco, CA, USA.
OMNI Biomarker Development, Genentech Inc. South SanFrancisco, CA, USA.

Allen Nguyen (A)

Biomarker Discovery, OMNI, Genentech Inc. South SanFrancisco, CA, USA.
OMNI Biomarker Development, Genentech Inc. South SanFrancisco, CA, USA.

Jacqueline M McBride (JM)

Biomarker Discovery, OMNI, Genentech Inc. South SanFrancisco, CA, USA.
OMNI Biomarker Development, Genentech Inc. South SanFrancisco, CA, USA.

Guo-Cheng Yuan (GC)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA.

Jean Frederic Colombel (JF)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jerome C Martin (JC)

Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Carmen Argmann (C)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA.

Mayte Suárez-Fariñas (M)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA.

Francesca Petralia (F)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA.

Saurabh Mehandru (S)

Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Classifications MeSH