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Pulmonary allergic responses augment interleukin-13 secretion by circulating basophils yet suppress interferon-α from plasmacytoid dendritic cells

Authors


Correspondence:
John T. Schroeder, Unit Office 2, The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
E-mail: schray@jhmi.edu

Summary

Background Allergic inflammatory processes may have the capacity to propagate systemically through the actions of circulating leucocytes. Consequently, basophils from allergic individuals are often ‘primed’, as evidenced by their hyperresponsiveness in vitro. IFN-α secreted predominantly by plasmacytoid dendritic cells (pDCs), suppresses basophil priming for IL-13 production in vitro.

Objective This study sought in vivo correlates arising during experimental allergen challenge that support an ‘axis-interplay’ between basophils and pDCs.

Methods Using segmental allergen challenge (SAC) in the lung, the immune responses of both cell types from the blood were investigated in volunteers (n=10) before and 24 h after allergen exposure. These responses were then correlated with inflammatory parameters measured in bronchoalveolar lavage fluids (BALF).

Results In the blood, SAC significantly augmented IL-13 secretion by basophils induced by IL-3 (P=0.009), yet reduced IFN-α secreted by pDCs stimulated with CpG (P=0.018). Both parameters were negatively correlated (P=0.0015), at least among those subjects that secreted the latter. Circulating basophil IL-13 responses further correlated with post-SAC bronchoalveolar lavage (BAL) parameters including IL-13 protein (P=0.04), basophil (P=0.051), eosinophil (P=0.0018), and total cell counts (P<0.003). Basophil and IL-13 levels in BAL correlated likewise (P=0.0002).

Conclusions These results support a mechanism of immune regulation whereby an allergen reduces innate immune responses and IFN-α production by pDCs, resulting in an enhanced inflammation and basophil cytokine production at sites of allergen exposure.

Cite this as: J. T. Schroeder, A. P. Bieneman, K. L. Chichester, L. Breslin, H. Xiao and M. C. Liu, Clinical & Experimental Allergy, 2010 (40) 745–754.

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