IL-10 Neutralization Attenuates Mast Cell Responses in a Murine Model of Experimental Food Allergy

Overview

Journal Immunohorizons

Specialty Allergy & Immunology

Date 2024 Jun 18

PMID 38888412

Authors

Dylan Krajewski

Saurav Ranjitkar

Caitlin Tedeschi

Nicole Maldonado Perez

Nathan Jordan

Mohamed Mire

Sallie S Schneider

Clinton B Mathias

Affiliations

Soon will be listed here.

Abstract

IgE-mediated mast cell (MC) activation is a critical component of allergic responses to oral Ags. Several T cell-derived cytokines have been shown to promote MC reactivity, and we recently demonstrated a critical role for the cytokine IL-10 in mediating MC responses during food allergy. In this study, we further validate the role of IL-10 using Ab-mediated IL-10 depletion. IL-10 neutralization significantly attenuated MC responses, leading to decreased MC accumulation and activation, as well as inhibition of MC-mediated symptoms such as allergic diarrhea. This was accompanied by decreased Th2 cytokine gene expression, attenuated systemic T cell responses, and fewer CD4 T cells, B cells, and MCs in the spleen. Our data further confirm the role of IL-10 in driving MC responses and suggest that IL-10-responsive MCs may constitute an important player in allergic responses.

Citing Articles

IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy.

Krajewski D, Ranjitkar S, Jordan N, Schneider S, Mathias C Front Immunol. 2025; 16:1526498.

PMID: 39935481 PMC: 11810977. DOI: 10.3389/fimmu.2025.1526498.

References

Stark K, Falkowski N, Brown C, McDonald R, Huffnagle G . Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model. Front Allergy. 2022; 3:851993. PMC: 9234882. DOI: 10.3389/falgy.2022.851993. View

Qian G, Jiang W, Sun D, Sun Z, Chen A, Fang H . B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3. Cell Mol Immunol. 2023; 20(11):1313-1327. PMC: 10616210. DOI: 10.1038/s41423-023-01079-w. View

Thompson-Snipes L, Dhar V, Bond M, Mosmann T, Moore K, Rennick D . Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med. 1991; 173(2):507-10. PMC: 2118779. DOI: 10.1084/jem.173.2.507. View

Ghildyal N, McNeil H, Stechschulte S, Austen K, Silberstein D, Gurish M . IL-10 induces transcription of the gene for mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells of Trichinella spiralis-infected mice. J Immunol. 1992; 149(6):2123-9. View

van Roon J, Wijngaarden S, Lafeber F, Damen C, van de Winkel J, Bijlsma J . Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol. 2003; 30(4):648-51. View

Akdis M, Akdis C . Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014; 133(3):621-31. DOI: 10.1016/j.jaci.2013.12.1088. View

Stevens R, Friend D, McNeil H, SCHILLER V, Ghildyal N, Austen K . Strain-specific and tissue-specific expression of mouse mast cell secretory granule proteases. Proc Natl Acad Sci U S A. 1994; 91(1):128-32. PMC: 42899. DOI: 10.1073/pnas.91.1.128. View

El Ansari Y, Kanagaratham C, Oettgen H . Mast Cells as Regulators of Adaptive Immune Responses in Food Allergy. Yale J Biol Med. 2020; 93(5):711-718. PMC: 7757069. View

Kosaka S, Tamauchi H, Terashima M, Maruyama H, Habu S, Kitasato H . IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation. Immunobiology. 2011; 216(7):811-20. DOI: 10.1016/j.imbio.2010.12.003. View

10.

Rennick D, Hunte B, Dang W, Thompson-Snipes L, Hudak S . Interleukin-10 promotes the growth of megakaryocyte, mast cell, and multilineage colonies: analysis with committed progenitors and Thy1loSca1+ stem cells. Exp Hematol. 1994; 22(2):136-41. View

11.

Xie M, Chen Q, Liu H, Yang K, Koh B, Wu H . T follicular regulatory cells and IL-10 promote food antigen-specific IgE. J Clin Invest. 2020; 130(7):3820-3832. PMC: 7324176. DOI: 10.1172/JCI132249. View

12.

Kinney S, Carlson L, Ser-Dolansky J, Thompson C, Shah S, Gambrah A . Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy. PLoS One. 2015; 10(7):e0132467. PMC: 4493063. DOI: 10.1371/journal.pone.0132467. View

13.

Makela M, Kanehiro A, Borish L, Dakhama A, Loader J, Joetham A . IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proc Natl Acad Sci U S A. 2000; 97(11):6007-12. PMC: 18549. DOI: 10.1073/pnas.100118997. View

14.

Tomar S, Hogan S . Recent advances in mechanisms of food allergy and anaphylaxis. F1000Res. 2020; 9. PMC: 7401090. DOI: 10.12688/f1000research.25638.1. View

15.

Toyoshima S, Wakamatsu E, Ishida Y, Obata Y, Kurashima Y, Kiyono H . The spleen is the site where mast cells are induced in the development of food allergy. Int Immunol. 2017; 29(1):31-45. DOI: 10.1093/intimm/dxx005. View

16.

Krajewski D, Kaczenski E, Rovatti J, Polukort S, Thompson C, Dollard C . Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses. Front Immunol. 2018; 9:2414. PMC: 6206211. DOI: 10.3389/fimmu.2018.02414. View

17.

Peng H, Wang W, Zhou M, Li R, Pan H, Ye D . Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol. 2013; 32(9):1255-66. DOI: 10.1007/s10067-013-2294-3. View

18.

Sellon R, Tonkonogy S, Schultz M, Dieleman L, Grenther W, Balish E . Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998; 66(11):5224-31. PMC: 108652. DOI: 10.1128/IAI.66.11.5224-5231.1998. View

19.

Lauw F, Pajkrt D, Hack C, Kurimoto M, van Deventer S, van der Poll T . Proinflammatory effects of IL-10 during human endotoxemia. J Immunol. 2000; 165(5):2783-9. DOI: 10.4049/jimmunol.165.5.2783. View

20.

Nedelkopoulou N, Taparkou A, Raftopoulou S, Gidaris D, Xinias I, Mavroudi A . Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population. Pediatr Allergy Immunol. 2020; 32(3):552-559. DOI: 10.1111/pai.13407. View