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Article ; Online: Animal models of eosinophilic esophagitis.

Pilat, Jennifer M / Jacobse, Justin / Buendia, Matthew A / Choksi, Yash A

2024

Abstract: Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. Over the past 25 yr, great strides have been made toward understanding its pathogenesis, in part due to studies in several types of animal models. The vast majority of these ... ...

Abstract	Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. Over the past 25 yr, great strides have been made toward understanding its pathogenesis, in part due to studies in several types of animal models. The vast majority of these models have been characterized in mice. In this review, we summarize the histopathological features of eosinophilic esophagitis recapitulated by these animal models, as well as discuss their strengths and weaknesses.
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiae043
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Article ; Online: A method for scoring 4-nitroquinoline 1-oxide-induced murine esophageal squamous neoplasia.

Aziz, Zaryab / Washington, Mary Kay / Jacobse, Justin / Choksi, Yash

Veterinary pathology

2023 Volume 60, Issue 3, Page(s) 384–393

Abstract: A mouse model for esophageal squamous cell carcinoma (ESCC) is induced by oral administration of the carcinogen 4-nitroquinoline 1-oxide (4-NQO). There is not an objective method for determining histopathologic severity of disease in this model. We aim ... ...

Abstract	A mouse model for esophageal squamous cell carcinoma (ESCC) is induced by oral administration of the carcinogen 4-nitroquinoline 1-oxide (4-NQO). There is not an objective method for determining histopathologic severity of disease in this model. We aim to create a clearly defined and easily applied scoring system that can quantify the severity of 4-NQO-induced murine ESCC. Fifteen wild-type C57BL/6J mice were treated with 4-NQO for 8 (n = 8) or 16 (n = 7) weeks, while the rest (n = 9) were treated with vehicle, as 8 weeks of 4-NQO typically results in dysplasia and 16 weeks in carcinoma. We identified histologic abnormalities of the esophagus in this model and developed metrics to grade severity of dysplasia, papillomas, and invasion. Scores were then calculated using quantitative digitized image analysis for measuring depth and extent of each feature within the entire sample. Each feature was also assigned a weight based on its relation to cancer severity. Histology scores were significantly different in the three groups, suggesting that this method can discriminate dysplasia from carcinoma. This model can be applied to any mouse treated with 4-NQO.
MeSH term(s)	Mice ; Animals ; Esophageal Neoplasms/chemically induced ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/veterinary ; Esophageal Squamous Cell Carcinoma/veterinary ; 4-Nitroquinoline-1-oxide/adverse effects ; Oxides/adverse effects ; Mice, Inbred C57BL ; Carcinogens ; Carcinoma/veterinary
Chemical Substances	4-Nitroquinoline-1-oxide (56-57-5) ; Oxides ; Carcinogens
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858231151381
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Article ; Online: A method for scoring 4-nitroquinoline 1-oxide-induced murine esophageal squamous neoplasia

Aziz, Zaryab / Washington, Mary Kay / Jacobse, Justin / Choksi, Yash

Veterinary Pathology. 2023 May, v. 60, no. 3 p.384-393

2023

Abstract	A mouse model for esophageal squamous cell carcinoma (ESCC) is induced by oral administration of the carcinogen 4-nitroquinoline 1-oxide (4-NQO). There is not an objective method for determining histopathologic severity of disease in this model. We aim to create a clearly defined and easily applied scoring system that can quantify the severity of 4-NQO-induced murine ESCC. Fifteen wild-type C57BL/6J mice were treated with 4-NQO for 8 (n = 8) or 16 (n = 7) weeks, while the rest (n = 9) were treated with vehicle, as 8 weeks of 4-NQO typically results in dysplasia and 16 weeks in carcinoma. We identified histologic abnormalities of the esophagus in this model and developed metrics to grade severity of dysplasia, papillomas, and invasion. Scores were then calculated using quantitative digitized image analysis for measuring depth and extent of each feature within the entire sample. Each feature was also assigned a weight based on its relation to cancer severity. Histology scores were significantly different in the three groups, suggesting that this method can discriminate dysplasia from carcinoma. This model can be applied to any mouse treated with 4-NQO.
Keywords	animal pathology ; carcinogens ; esophagus ; histology ; histopathology ; image analysis ; mice ; models ; oral administration ; squamous cell carcinoma ; digestive tract ; disease severity metrics ; esophageal squamous cell cancer ; mouse model
Language	English
Dates of publication	2023-05
Size	p. 384-393.
Publishing place	SAGE Publications
Document type	Article ; Online
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858231151381
Database	NAL-Catalogue (AGRICOLA)

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Article: Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome.

Rajagopala, Seesandra V / Shilts, Meghan H / Correa, Hernan / Das, Suman R / Choksi, Yash A / Jacobse, Justin / Goettel, Jeremy A / Hiremath, Girish

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG

2023 Volume 28, Issue 6, Page(s) 504–508

Abstract: Objective: Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children ... ...

Abstract	Objective: Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. Methods: Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI-], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. Results: The median (IQR) age of our cohort was 14 years (12-16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI-, the PPI+ had upregulation of 27 genes including the Conclusions: In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.
Language	English
Publishing date	2023-10-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028543-4
ISSN	1551-6776
ISSN	1551-6776
DOI	10.5863/1551-6776-28.6.504
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Article: Distinct roles for interleukin-23 receptor signaling in regulatory T cells in sporadic and inflammation-associated carcinogenesis.

Jacobse, Justin / Pilat, Jennifer M / Li, Jing / Brown, Rachel E / Kwag, Aaron / Buendia, Matthew A / Choksi, Yash A / Washington, M Kay / Williams, Christopher S / Markham, Nicholas O / Short, Sarah P / Goettel, Jeremy A

Frontiers in oncology

2024 Volume 13, Page(s) 1276743

Abstract: Introduction: The pro-inflammatory cytokine interleukin-23 (IL-23) has been implicated in colorectal cancer (CRC). Yet, the cell-specific contributions of IL-23 receptor (IL-23R) signaling in CRC remain unknown. One of the cell types that highly ... ...

Abstract	Introduction: The pro-inflammatory cytokine interleukin-23 (IL-23) has been implicated in colorectal cancer (CRC). Yet, the cell-specific contributions of IL-23 receptor (IL-23R) signaling in CRC remain unknown. One of the cell types that highly expresses IL-23R are colonic regulatory T cells (Treg cells). The aim of this study was to define the contribution of Treg cell-specific IL-23R signaling in sporadic and inflammation-associated CRC. Methods: In mice, the role of IL-23R in Treg cells in colitis-associated cancer (CAC) was investigated using azoxymethane/dextran sodium sulphate in wild-type Treg cell reporter mice (WT, Results: In CAC, Conclusion: Inflammation in colorectal carcinogenesis differs with respect to the contribution of IL-23R signaling in regulatory T cells.
Language	English
Publishing date	2024-02-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1276743
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Article ; Online: Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease.

Jacobse, Justin / Li, Jing / Rings, Edmond H H M / Samsom, Janneke N / Goettel, Jeremy A

Frontiers in immunology

2021 Volume 12, Page(s) 716499

Abstract: ... ...

Abstract	FOXP3
MeSH term(s)	Animals ; Antigens/immunology ; Apoptosis/immunology ; Biomarkers ; Cell Communication ; Cellular Microenvironment/immunology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Susceptibility ; Gastrointestinal Microbiome/immunology ; Genetic Predisposition to Disease ; Homeostasis ; Humans ; Immunity, Mucosal ; Immunomodulation ; Inflammatory Bowel Diseases/etiology ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Mucosal-Associated Invariant T Cells/immunology ; Mucosal-Associated Invariant T Cells/metabolism ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tretinoin/metabolism
Chemical Substances	Antigens ; Biomarkers ; Receptors, Antigen, T-Cell ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2021-08-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.716499
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Article ; Online: Sleep Leads to Brain-Wide Neural Changes Independent of Allocentric and Egocentric Spatial Training in Humans and Rats.

Samanta, Anumita / van Rongen, Laurens S / Rossato, Janine I / Jacobse, Justin / Schoenfeld, Robby / Genzel, Lisa

Cerebral cortex (New York, N.Y. : 1991)

2021 Volume 31, Issue 11, Page(s) 4970–4985

Abstract: Sleep is important for memory consolidation and systems consolidation in particular, which is thought to occur during sleep. While there has been a significant amount of research regarding the effect of sleep on behavior and certain mechanisms during ... ...

Abstract	Sleep is important for memory consolidation and systems consolidation in particular, which is thought to occur during sleep. While there has been a significant amount of research regarding the effect of sleep on behavior and certain mechanisms during sleep, evidence that sleep leads to consolidation across the system has been lacking until now. We investigated the role of sleep in the consolidation of spatial memory in both rats and humans using a watermaze task involving allocentric- and egocentric-based training. Analysis of immediate early gene expression in rodents, combined with functional magnetic resonance imaging in humans, elucidated similar behavioral and neural effects in both species. Sleep had a beneficial effect on behavior in rats and a marginally significant effect in humans. Interestingly, sleep led to changes across multiple brain regions at the time of retrieval in both species and in both training conditions. In rats, sleep led to increased gene expression in the hippocampus, striatum, and prefrontal cortex. In the humans, sleep led to an activity increase in brain regions belonging to the executive control network and a decrease in activity in regions belonging to the default mode network. Thus, we provide cross-species evidence for system-level memory consolidation occurring during sleep.
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Hippocampus/diagnostic imaging ; Humans ; Memory Consolidation ; Prefrontal Cortex ; Rats ; Sleep
Language	English
Publishing date	2021-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhab135
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Article: MTGR1 is required to maintain small intestinal stem cell populations.

Williams, Christopher / Brown, Rachel / Zhao, Yue / Wang, Jing / Chen, Zhengyi / Blunt, Koral / Pilat, Jennifer / Parang, Bobak / Choksi, Yash / Lau, Ken / Hiebert, Scott / Short, Sarah / Jacobse, Justin / Xu, Yanwen / Yang, Yilin / Goettel, Jeremy

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2023

Abstract: Undifferentiated intestinal stem cells (ISCs), particularly those marked ... ...

Abstract	Undifferentiated intestinal stem cells (ISCs), particularly those marked by
Language	English
Publishing date	2023-09-21
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3315071/v1
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Article ; Online: A synthesis and subgroup analysis of the eosinophilic esophagitis tissue transcriptome.

Jacobse, Justin / Brown, Rachel / Revetta, Frank / Vaezi, Michael / Buendia, Matthew A / Williams, Christopher S / Higginbotham, Tina / Washington, M Kay / Goettel, Jeremy / Hiremath, Girish / Choksi, Yash A

The Journal of allergy and clinical immunology

2023 Volume 153, Issue 3, Page(s) 759–771

Abstract: Background: Eosinophilic esophagitis (EoE) is a chronic immune mediated inflammatory disorder of the esophagus. It is still unknown why children and adults present differently, and there is little evidence about why it is more common in men than women.!# ...

Abstract	Background: Eosinophilic esophagitis (EoE) is a chronic immune mediated inflammatory disorder of the esophagus. It is still unknown why children and adults present differently, and there is little evidence about why it is more common in men than women. Objective: Our aim was to synthesize published and unpublished esophageal bulk RNA-sequencing (RNA-seq) data to gain novel insights into the pathobiology of EoE and examine the differences in EoE transcriptome by sex and age group. Methods: Esophageal bulk RNA-seq data from 5 published and 2 unpublished studies resulting in 137 subjects (EoE: N = 76; controls: N = 61) were analyzed. For overall analysis, combined RNA-seq data of patients with EoE were compared with those of controls and subgroup analysis was conducted in patients with EoE by age of the patient (children [<18 years] vs adults [≥18 years]) and sex (female vs male). Gene-set enrichment analysis, ingenuity pathway analysis (IPA), cell-type analysis, immunohistochemistry, and T-cell or B-cell receptor analysis were performed. Results: Overall analysis identified dysregulation of new genes in EoE compared with controls. IPA revealed that EoE is characterized by a mixed inflammatory response compared with controls. Cell-type analysis showed that cell composition varied with age: children had more mast cells, whereas adults had more macrophages. Finally, gene-set enrichment analysis and IPA revealed pathways that were differentially regulated in adults versus children and male versus female patients with EoE. Conclusions: Using a unique approach to analyze bulk RNA-seq data, we found that EoE is characterized by a mixed inflammatory response, and the EoE transcriptome may be influenced by age and sex. These findings enhance insights into the molecular mechanisms of EoE.
MeSH term(s)	Child ; Adult ; Humans ; Male ; Female ; Adolescent ; Eosinophilic Esophagitis/genetics ; Transcriptome ; Immunohistochemistry ; RNA
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.10.002
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Article ; Online: HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice.

Tyagi, Rajeev K / Jacobse, Justin / Li, Jing / Allaman, Margret M / Otipoby, Kevin L / Sampson, Erik R / Wilson, Keith T / Goettel, Jeremy A

Frontiers in immunology

2021 Volume 12, Page(s) 630204

Abstract: Regulatory T ( ... ...

Abstract	Regulatory T (T
Language	English
Publishing date	2021-02-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.630204
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