Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning and Predisposes to Oral Antigen Sensitization in Mice

Frontiers in Immunology

Senad Divanovic¹  Rodney D. Newberry²  Gary B. Huffnagle³  Jee-Boong Lee⁶  Christopher A. Brown⁸  Varsha Ganesan⁹  Simon P. Hogan⁹  Taeko K. Noah⁹  Sunil Tomar⁹  Amnah Yamani⁹ 

[1] Center for Inflammation and Tolerance, Cincinnati Children’s Medical Center, Cincinnati, OH, United States;Department of Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States;Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, United States;Department of Pathology, University of Michigan, Ann Arbor, MI, United States;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Division of Allergy and Immunology, Cincinnati Children’s Medical Center, Cincinnati, OH, United States;Division of Immunobiology, Cincinnati Children’s Medical Center, Cincinnati, OH, United States;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States;Mary H Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI, United States;

关键词: food sensitization;    mouse models;    antigen passage;    thermoneutral conditions;    food allergy;   

DOI  :  10.3389/fimmu.2021.636198

来源: DOAJ

【 摘 要 】

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26–30°C) – has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18–20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium via goblet cell antigen passages (GAPs). In contrast, food allergy sensitive Il4raF709 mice housed under standard temperature conditions translocated the luminal antigens in the SI across the epithelium via secretory antigen passages (SAPs). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg allergens at standard temperature predisposed Il4raF709 mice to develop an anaphylactic reaction. Housing Il4raF709 mice at Tn altered systemic type 2 cytokine, IL-4, and the landscape of SI antigen passage patterning (villus and crypt involvement). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg antigen under Tn conditions led to the robust induction of egg-specific IgE and development of food-induced mast cell activation and hypovolemic shock. Similarly, Tn housing of WT BALB/c mice altered the cellular patterning of SI antigen passage (GAPs to SAPs). Activation of SI antigen passages and the oral challenge of WT BALB/c mice with egg antigen led to systemic reactivity to egg and mast cell activation. Together these data demonstrate that Tn housing alters antigen passage cellular patterning and landscape, and concurrent oral exposure of egg antigens and SAP activation is sufficient to induce oral antigen sensitization.

【 授权许可】

Unknown