| First Author | Rothenberg ME | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 9 | Pages | 4873-80 |
| PubMed ID | 21957151 | Mgi Jnum | J:179431 |
| Mgi Id | MGI:5302425 | Doi | 10.4049/jimmunol.1004159 |
| Citation | Rothenberg ME, et al. (2011) il-13 receptor alpha1 differentially regulates aeroallergen-induced lung responses. J Immunol 187(9):4873-80 |
| abstractText | IL-13 and IL-4 are hallmark cytokines of Th2-associated diseases including asthma. Recent studies revealed that IL-13Ralpha1 regulates asthma pathogenesis by mediating both IL-4- and IL-13-mediated responses. Nonetheless, the relative contribution of each cytokine in response to aeroallergen challenge and the degree of functional dichotomy between IL-4 and IL-13 in asthma remains unclear. Consistent with prior publications, we demonstrate that IL-13Ralpha1 regulates aeroallergen-induced airway resistance and mucus production but not IgE and Th2 cytokine production. We demonstrate that aeroallergen-induced eosinophil recruitment and chemokine production were largely dependent on IL-13Ralpha1 after Aspergillus but not house dust mite (HDM) challenges. Notably, Aspergillus-challenged mice displayed increased IL-13Ralpha1-dependent accumulation of dendritic cell subsets into lung-draining lymph nodes in comparison with HDM-challenged mice. Comparison of IL-4 and IL-13 levels in the different experimental models revealed increased IL-4/IL-13 ratios after HDM challenge, likely explaining the IL-13Ralpha1-independent eosinophilia and chemokine production. Consistently, eosinophil adoptive transfer experiments revealed near ablation of lung eosinophilia in response to Aspergillus in Il13ra1(-/-) mice, suggesting that Aspergillus-induced lung eosinophil recruitment is regulated by IL-13-induced chemokine production rather than altered IL-13 signaling in eosinophils. Furthermore, the near complete protection observed in Il13ra1(-/-) mice in response to Aspergillus challenge was dependent on mucosal sensitization, as alum/Aspergillus-sensitized mice that were rechallenged with Aspergillus developed IL-13Ralpha1-independent eosinophilia although other asthma parameters remained IL-13Ralpha1 dependent. These results establish that IL-13Ralpha1 is required for aeroallergen-induced airway resistance and that allergen-induced chemokine production and consequent eosinophilia is dictated by the balance between IL-4 and IL-13 production in situ. |
