Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma.

Carolin Boehne,Thomas Kamradt,Gesine Hansen,Sebastian Drube,Almut Meyer-Bahlburg,Martin Boettcher,Ann-Kathrin Behrendt,Svetlana P Chapoval

doi:10.1371/journal.pone.0249605

Abstract

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been described as a transmembrane protein, expressed on the surface of various T cells as well as different cells of innate immunity. It has since been associated with Th1 mediated autoimmune diseases and transplantation tolerance studies, thereby indicating a possible role of this receptor in counter-regulation of Th2 immune responses. In the present study we therefore directly examined the role of Tim-3 in allergic inflammation and respiratory tolerance. First, Tim-3-/- mice and wild type controls were immunized and challenged with the model allergen ovalbumin (OVA) to induce an asthma-like phenotype. Analysis of cell numbers and distribution in the bronchoalveolar lavage (BAL) fluid as well as lung histology in H&E stained lung sections demonstrated a comparable degree of eosinophilic inflammation in both mouse strains. Th2 cytokine production in restimulated cell culture supernatants and serum IgE and IgG levels were equally increased in both genotypes. In addition, cell proliferation and the distribution of different T cell subsets were comparable. Moreover, analysis of both mouse strains in our respiratory tolerance model, where mucosal application of the model allergen before immunization, prevents the development of an asthma-like phenotype, revealed no differences in any of the parameters mentioned above. The current study demonstrates that Tim-3 is dispensable not only for the development of allergic inflammation but also for induction of respiratory tolerance in mice in an OVA-based model.

Highlights

Within the last decades the prevalence of allergic asthma has risen steadily in western countries affecting more than 300 million people worldwide
T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) is dispensable for the development of allergic airway inflammation in mice
Mice, immunized and challenged with the model allergen OVA according to the protocol described above, develop an allergic phenotype characterized by an eosinophilic airway inflammation, high allergen-specific serum IgE levels as well as increased Th2 cytokine production (OVA) compared to control animals (Alum) [7, 9, 34] (Figs 2 and 3)

Summary

Introduction

Within the last decades the prevalence of allergic asthma has risen steadily in western countries affecting more than 300 million people worldwide . It is a very common chronic lung disease that is characterized by eosinophilic airway inflammation, airway hyperreactivity and reversible airway obstruction [1]. About 50% of patients are characterized by a type- 2 high immune status involving innate as well as adaptive immune cells [2]. The latter is defined by a Th2 dominated cell environment insufficiently counterbalanced by Th1 as well as Treg cells [3, 4]. We and others have highlighted the role of T cell surface expressed proteins such as costimulatory or coinhibitory molecules in the modulation of allergic immune reaction [5,6,7,8,9,10,11]

Methods

Results

Conclusion