Significance of Interleukin (IL)-15 in IgE Associated Eosinophilic Esophagitis (EoE)

Overview

Journal Int J Basic Clin Immunol

Date 2020 Apr 17

PMID 32296783

Citations 4

Authors

Sathisha Upparahalli Venkateshaiah

Hemanth Kumar Kandikattu

Anil Mishra

Affiliations

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Abstract

Background And Aim: IgE-mediated immune responses contribute to the pathogenesis of eosinophilic esophagitis (EoE). Interleukin (IL)-4 is a well-established cytokine involved in B cell activation, immunoglobulin (Ig) E production and isotype class switching. Earlier reports indicated that IL-15, B cells and IgE are induced in EoE pathogenesis. Therefore, we hypothesized that induced IL-15 and IgE may have a significant correlation in promoting EoE pathogenesis.

Methods: Accordingly, we performed ELISA, qPCR, flowcytometric and immunostaining analyses to examine IgE, B cells, eosinophils and mast cells in the esophagus of IL-15 overexpressed mice following EoE induction.

Results: Herein, we show that IL-15 overexpressed mice indeed have induced baseline IL-4, B cells, eosinophils, mast cells and IgE levels in the blood and esophagus. Further, we observed that IL-15 overexpressed mice show induction of IgE, and accumulation of degranulated eosinophils and mast cells in allergen-induced experimental EoE. Notably, despite induced blood IgE, esophageal eosinophilia is not induced in intestinal fatty acid binding protein IL-15 overexpressed gene (Fabpi-IL-15) mice. Fabpi-IL-15 transgenic mice showed IgE in the blood and intestine and intestinal eosinophilia, but no esophageal eosinophilia at baseline and comparable eosinophils in the esophagus of saline and allergen challenged Fabpi-IL-15 mice. Similarly, allergen challenged gene-deficient mice show reduced IgE and esophageal eosinophilia in allergen-induced experimental EoE.

Conclusions: Taken together, we for the first time provide direct evidence that tissue-specific IL-15 induced IgE mediated responses, not systemic IgE is critical in promoting EoE pathogenesis.

Citing Articles

From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis.

Barchi A, Mandarino F, Yacoub M, Albarello L, Massimino L, Savarino E Biomolecules. 2024; 14(9).

PMID: 39334846 PMC: 11429508. DOI: 10.3390/biom14091080.

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.

Racca F, Pellegatta G, Cataldo G, Vespa E, Carlani E, Pelaia C Front Physiol. 2022; 12:815842.

PMID: 35095572 PMC: 8790151. DOI: 10.3389/fphys.2021.815842.

Blood mRNA levels of T cells and IgE receptors are novel non-invasive biomarkers for eosinophilic esophagitis (EoE).

Upparahalli Venkateshaiah S, Rayapudi M, Kandikattu H, Yadavalli C, Mishra A Clin Immunol. 2021; 227:108752.

PMID: 33945873 PMC: 8215583. DOI: 10.1016/j.clim.2021.108752.

Tacrolimus (FK506) treatment protects allergen-, IL-5- and IL-13-induced mucosal eosinophilia.

Kandikattu H, Upparahalli Venkateshaiah S, Verma A, Mishra A Immunology. 2021; 163(2):220-235.

PMID: 33512727 PMC: 8114213. DOI: 10.1111/imm.13314.

References

Mishra A, Hogan S, Lee J, Foster P, Rothenberg M . Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest. 1999; 103(12):1719-27. PMC: 408388. DOI: 10.1172/JCI6560. View

Mishra A, Schlotman J, Wang M, Rothenberg M . Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2006; 81(4):916-24. DOI: 10.1189/jlb.1106653. View

Noti M, Tait Wojno E, Kim B, Siracusa M, Giacomin P, Nair M . Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis. Nat Med. 2013; 19(8):1005-13. PMC: 3951204. DOI: 10.1038/nm.3281. View

Jyonouchi S, Smith C, Saretta F, Abraham V, Ruymann K, Modayur-Chandramouleeswaran P . Invariant natural killer T cells in children with eosinophilic esophagitis. Clin Exp Allergy. 2013; 44(1):58-68. PMC: 3926503. DOI: 10.1111/cea.12201. View

Spergel J . Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol. 2007; 7(3):274-8. DOI: 10.1097/ACI.0b013e32813aee4a. View

Liacouras C, Furuta G, Hirano I, Atkins D, Attwood S, Bonis P . Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011; 128(1):3-20.e6. DOI: 10.1016/j.jaci.2011.02.040. View

Giri J, Anderson D, Kumaki S, Park L, Grabstein K, Cosman D . IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2. J Leukoc Biol. 1995; 57(5):763-6. DOI: 10.1002/jlb.57.5.763. View

Safroneeva E, Straumann A, Coslovsky M, Zwahlen M, Kuehni C, Panczak R . Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis. Gastroenterology. 2015; 150(3):581-590.e4. PMC: 6011000. DOI: 10.1053/j.gastro.2015.11.004. View

Niranjan R, Mavi P, Rayapudi M, Dynda S, Mishra A . Pathogenic role of mast cells in experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol. 2013; 304(12):G1087-94. PMC: 3680716. DOI: 10.1152/ajpgi.00070.2013. View

10.

Matthews A, Friend D, Zimmermann N, Sarafi M, Luster A, Pearlman E . Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci U S A. 1998; 95(11):6273-8. PMC: 27654. DOI: 10.1073/pnas.95.11.6273. View

11.

Vicario M, Blanchard C, Stringer K, Collins M, Mingler M, Ahrens A . Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut. 2009; 59(1):12-20. PMC: 2791234. DOI: 10.1136/gut.2009.178020. View

12.

Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K . CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997; 278(5343):1626-9. DOI: 10.1126/science.278.5343.1626. View

13.

Mavi P, Niranjan R, Dutt P, Zaidi A, Shukla J, Korfhagen T . Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol. 2014; 307(5):G499-507. PMC: 4154121. DOI: 10.1152/ajpgi.00141.2014. View

14.

Mishra A, Hogan S, Brandt E, Rothenberg M . An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001; 107(1):83-90. PMC: 198543. DOI: 10.1172/JCI10224. View

15.

Rajavelu P, Rayapudi M, Moffitt M, Mishra A, Mishra A . Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol. 2011; 302(7):G645-54. PMC: 3330778. DOI: 10.1152/ajpgi.00223.2011. View

16.

Rayapudi M, Mavi P, Zhu X, Pandey A, Abonia J, Rothenberg M . Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2010; 88(2):337-46. PMC: 2908938. DOI: 10.1189/jlb.0110025. View

17.

Lucendo A, Arias A, Tenias J . Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014; 113(6):624-9. DOI: 10.1016/j.anai.2014.08.004. View

18.

Armitage R, Macduff B, Eisenman J, Paxton R, Grabstein K . IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. J Immunol. 1995; 154(2):483-90. View

19.

Lexmond W, Neves J, Nurko S, Olszak T, Exley M, Blumberg R . Involvement of the iNKT cell pathway is associated with early-onset eosinophilic esophagitis and response to allergen avoidance therapy. Am J Gastroenterol. 2014; 109(5):646-57. PMC: 4132949. DOI: 10.1038/ajg.2014.12. View

20.

Leadbetter E, Brigl M, Illarionov P, Cohen N, Luteran M, Pillai S . NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci U S A. 2008; 105(24):8339-44. PMC: 2448838. DOI: 10.1073/pnas.0801375105. View