BACKGROUND: The effect of increased age on the induction of oral tolerance by low-dose antigen feeding and its effect on the response to antigen airway challenge in aged mice have not been well characterized. OBJECTIVE: To determine whether oral tolerance can be induced in aged mice and its impact on the development of allergic airway inflammation. METHODS: Younger (6 weeks old) and aged (18 months old) mice were fed ovalbumin (OVA) prior to sensitization to induce antigen tolerance. Serum antigen-specific immunoglobulins (Igs), bronchoalveolar lavage fluid (BALF), lung histology, enumeration of CD4 + Foxp3+ Treg cells, and airway hyperresponsiveness (AHR) were determined after the final antigen challenge. RESULTS: Feeding antigen to aged mice prior to sensitization induced oral tolerance as determined by a decrease in antigen-specific IgE and IgG(1); however, the effect was greater in younger mice. Induction of oral tolerance was associated with a greater increase in airway Treg cells in the younger mice. Despite these differences, oral tolerance significantly suppressed features of asthma in aged mice, including BALF total cell and eosinophil numbers, cytokine production, and AHR. CONCLUSIONS: Aged mice developed oral tolerance to antigen, which suppressed several features of allergic airway inflammation.
BACKGROUND: The effect of increased age on the induction of oral tolerance by low-dose antigen feeding and its effect on the response to antigen airway challenge in aged mice have not been well characterized. OBJECTIVE: To determine whether oral tolerance can be induced in aged mice and its impact on the development of allergic airway inflammation. METHODS: Younger (6 weeks old) and aged (18 months old) mice were fed ovalbumin (OVA) prior to sensitization to induce antigen tolerance. Serum antigen-specific immunoglobulins (Igs), bronchoalveolar lavage fluid (BALF), lung histology, enumeration of CD4 + Foxp3+ Treg cells, and airway hyperresponsiveness (AHR) were determined after the final antigen challenge. RESULTS: Feeding antigen to aged mice prior to sensitization induced oral tolerance as determined by a decrease in antigen-specific IgE and IgG(1); however, the effect was greater in younger mice. Induction of oral tolerance was associated with a greater increase in airway Treg cells in the younger mice. Despite these differences, oral tolerance significantly suppressed features of asthma in aged mice, including BALF total cell and eosinophil numbers, cytokine production, and AHR. CONCLUSIONS: Aged mice developed oral tolerance to antigen, which suppressed several features of allergic airway inflammation.
Authors: Gwen S Skloot; Paula J Busse; Sidney S Braman; Elizabeth J Kovacs; Anne E Dixon; Carlos A Vaz Fragoso; Nicola Scichilone; Y S Prakash; Christina M Pabelick; Sameer K Mathur; Nicola A Hanania; Wendy C Moore; Peter G Gibson; Susan Zieman; Betina B Ragless Journal: Ann Am Thorac Soc Date: 2016-11
Authors: Prasanna M Chandramouleeswaran; Dawen Shen; Anna J Lee; Alain Benitez; Kara Dods; Fiona Gambanga; Benjamin J Wilkins; Jamie Merves; Yuliana Noah; Sarit Toltzis; Jennifer H Yearley; Jonathan M Spergel; Hiroshi Nakagawa; Rene deWaal Malefyt; Amanda B Muir; Mei-Lun Wang Journal: PLoS One Date: 2016-03-18 Impact factor: 3.240