Investigating the role of BAFF in murine models of allergic asthma

Introduction: The cytokine B cell activating factor of the TNF family (BAFF) is crucial for peripheral B cell survival. It is well known that elevated BAFF levels are associated with autoimmune diseases but its role in allergic diseases including asthma is barely understood. Aims and objectives: To better comprehend the role of BAFF in allergic asthma we analyzed BAFF in murine asthma models. Methods: Wildtype (WT) and B cell deficient (μMT) mice were immunized with ovalbumin (OVA) or house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) was measured morphometrically, airway hyperreactivity (AHR) by invasive lung function and BAFF via ELISA. Results: Asthmatic WT mice showing lung eosinophilia and severe AHR have significantly elevated BAFF serum levels compared to controls. Additionally, in OVA-induced respiratory tolerant mice, BAFF levels are lower than in allergic mice. Kinetic studies demonstrate that BAFF levels increase, the more often allergen is administered intranasally suggesting local BAFF production in the asthmatic lung. Furthermore, BAFF determination in BALF showed increased levels in allergic compared to control mice. To test, whether BAFF is related to elevated IgE levels during asthma, BAFF production in μMT mice was analyzed. Allergen treated μMT mice develop a similar allergic phenotype compared to WT mice and show increased BAFF levels in serum and BALF even in IgE absence. Conclusions: In asthma models, allergic mice show elevated systemic and local BAFF, which increases with frequency of allergen uptake via the lung and is independent of IgE presence. Thus, BAFF inhibition, recently permitted for treatment of systemic lupus erythematodes, might represent a new therapeutic target in asthma.