Lung Resident Cells Are Independently Capable of Maintaining Chronic Asthma in Mice After Immune Ablation

Christina Christianson, Chaoyu Chen, Magdalena Gorska, Rafeul Alam

Author address: 

National Jewish Health, Denver, CO

Abstract: 

Rationale

We developed a mouse model of chronic asthma where the asthma features persist for longer than 3 months after cessation of allergen exposure. The objective of this study was to assess the contribution of lung resident cells to the maintenance of asthma phenotype and to examine the signaling mechanisms.

Methods

Chronic asthma is induced through twice weekly intranasal exposure to a combination of allergens (D. Farinae, ragweed, and aspergillus) for six weeks. Two weeks after cessation of allergen exposure immune ablation was accomplished by lethal irradiation and irradiated mice underwent transplantation of naïve bone marrow. Airway hyperreactivity (airway resistance to inhaled methacholine by Flexivent) and immunohistological features were measured at weeks 2, 4 and 6 after irradiation.

Results

Mice from the chronic model maintained the typical features of chronic asthma—airway hyperreactivity and epithelial remodeling at all observation points following immune ablation. They also mounted de novo inflammation that was characteristically localized to the peribronchial and perivascular space. Control mice did not manifest any features of asthma. Persistence of asthma in the chronic model following immune ablation was associated with sustained activation of ERK1/2 and AKT signaling, especially in airway epithelium. To examine the importance of lung cell ERK1 for asthma we adoptive transferred immunized ERK1+/+ CD4 T cells to ERK1-/- and ERK1+/+ littermate control mice. Only ERK1+/+ but not ERK1-/- recipient mice developed asthma.

Conclusions

Lung resident cells can sustain chronic asthma in the absence of sensitized immune cells. Lung cell ERK1 plays a non-redundant role in the development of asthma

http://dx.doi.org/10.1016/j.jaci.2012.12.852

Journal of Allergy and Clinical Immunology, Vol. 131, Issue 2, AB48

abstract No: 

173
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