Local Type 2 Immunity in Eosinophilic Gastritis

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2023 Feb 8

PMID 36754294

Authors

Netali Ben-Baruch Morgenstern

Tetsuo Shoda

Yrina Rochman

Julie M Caldwell

Margaret H Collins

Vincent Mukkada

Philip E Putnam

Scott M Bolton

Jennifer M Felton

Mark Rochman

Cristin Murray-Petzold

Kara L Kliewer

Marc E Rothenberg

Affiliations

Soon will be listed here.

Abstract

Background: Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied.

Objective: We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology.

Methods: Gastric biopsy samples (n = 6 EoG, n = 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n = 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters.

Results: Gastric biopsy samples contained CD3 T cells that were mainly CD8; the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7 ± 3.0 and 4.3 ± 0.6, respectively; P = .28). Gastric regulatory T (CD3CD4FOXP3) and T2 (CD3CD4GATA3) cell levels were increased in EoG versus controls (2-fold, P < .05 and 10-fold, P < .001, respectively) and correlated with gastric eosinophil levels (r = 0.63, P < .05 and r = 0.85, P < .001, respectively), endoscopic pathology (r = 0.56, P < .01; r = 0.84, P < .001, respectively), and histopathology (r = 0.72, P < .01; r = 0.82, P < .01, respectively). Cytokine-positive, most notably IL-4, T2 cell levels strongly correlated with histologic and endoscopic scores (r = 0.82, P < .0001 and r = 0.78, P < .0001, respectively). In an independent EoG cohort (n = 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r = 0.22, P < .005; r = 0.54, P < .0001; and r = 0.36, P < .0001, respectively) and endoscopic score (r = 0.27, P < .001; r = 0.40, P < .0001; and r = 0.35, P < .0001, respectively).

Conclusions: EoG is a T2 cell-associated disease featuring increased gastric type 2 cytokine-producing CD3CD4GATA3T2 cells that strongly correlate with disease pathologies.

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References

Shoda T, Wen T, Caldwell J, Collins M, Besse J, Osswald G . Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study. J Allergy Clin Immunol. 2019; 145(1):255-269. PMC: 6949389. DOI: 10.1016/j.jaci.2019.11.007. View

Caldwell J, Collins M, Stucke E, Putnam P, Franciosi J, Kushner J . Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome. J Allergy Clin Immunol. 2014; 134(5):1114-24. PMC: 4254306. DOI: 10.1016/j.jaci.2014.07.026. View

Leon B, Ballesteros-Tato A . Modulating Th2 Cell Immunity for the Treatment of Asthma. Front Immunol. 2021; 12:637948. PMC: 7902894. DOI: 10.3389/fimmu.2021.637948. View

Assaad A, Gupta S, Collins M, Thomson M, Heath A, Smith D . An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011; 141(5):1593-604. DOI: 10.1053/j.gastro.2011.07.044. View

Barnes P . Therapeutic strategies for allergic diseases. Nature. 1999; 402(6760 Suppl):B31-8. DOI: 10.1038/35037026. View

Lwin T, Melton S, Genta R . Eosinophilic gastritis: histopathological characterization and quantification of the normal gastric eosinophil content. Mod Pathol. 2010; 24(4):556-63. DOI: 10.1038/modpathol.2010.221. View

Hirano I, Collins M, King E, Sun Q, Chehade M, Abonia J . Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort. Am J Gastroenterol. 2022; 117(3):413-423. PMC: 8897269. DOI: 10.14309/ajg.0000000000001625. View

Moawad F . Eosinophilic Esophagitis: Incidence and Prevalence. Gastrointest Endosc Clin N Am. 2017; 28(1):15-25. DOI: 10.1016/j.giec.2017.07.001. View

Redrup A, Howard B, MacGlashan Jr D, Lichtenstein L, Schroeder J . Differential regulation of IL-4 and IL-13 secretion by human basophils: their relationship to histamine release in mixed leukocyte cultures. J Immunol. 1998; 160(4):1957-64. View

10.

Rothenberg M . Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004; 113(1):11-28. DOI: 10.1016/j.jaci.2003.10.047. View

11.

Ben-Baruch Morgenstern N, Ballaban A, Wen T, Shoda T, Caldwell J, Kliewer K . Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission. J Allergy Clin Immunol. 2022; 149(6):2062-2077. PMC: 9177790. DOI: 10.1016/j.jaci.2022.02.025. View

12.

Hirano I, Collins M, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer A . RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis. Gastroenterology. 2018; 156(3):592-603.e10. DOI: 10.1053/j.gastro.2018.10.051. View

13.

Gonsalves N . Eosinophilic Gastrointestinal Disorders. Clin Rev Allergy Immunol. 2019; 57(2):272-285. DOI: 10.1007/s12016-019-08732-1. View

14.

Sato M, Shoda T, Shimizu H, Orihara K, Futamura K, Matsuda A . Gene Expression Patterns in Distinct Endoscopic Findings for Eosinophilic Gastritis in Children. J Allergy Clin Immunol Pract. 2017; 5(6):1639-1649.e2. DOI: 10.1016/j.jaip.2017.03.030. View

15.

Spergel J, Rothenberg M, Collins M, Furuta G, Markowitz J, Fuchs 3rd G . Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2011; 129(2):456-63, 463.e1-3. DOI: 10.1016/j.jaci.2011.11.044. View

16.

Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome J . Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity. 2012; 38(1):187-97. PMC: 3557604. DOI: 10.1016/j.immuni.2012.09.020. View

17.

Rothenberg M . Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. J Allergy Clin Immunol. 2022; 150(6):1325-1332. PMC: 9742179. DOI: 10.1016/j.jaci.2022.09.027. View

18.

Collins M, Capocelli K, Yang G . Eosinophilic Gastrointestinal Disorders Pathology. Front Med (Lausanne). 2018; 4:261. PMC: 5775510. DOI: 10.3389/fmed.2017.00261. View

19.

Cianferoni A, Spergel J . Eosinophilic Esophagitis and Gastroenteritis. Curr Allergy Asthma Rep. 2015; 15(9):58. DOI: 10.1007/s11882-015-0558-5. View

20.

Wu Z, Zheng Y, Sheng J, Han Y, Yang Y, Pan H . CD3CD4CD8 (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer. Front Immunol. 2022; 13:816005. PMC: 8866817. DOI: 10.3389/fimmu.2022.816005. View