کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2832537 | 1570745 | 2007 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Complement regulates inhalation tolerance at the dendritic cell/T cell interface Complement regulates inhalation tolerance at the dendritic cell/T cell interface](/preview/png/2832537.png)
Pulmonary exposure to innocuous aeroallergens is a common event leading to inhalation tolerance. Distinct subsets of pulmonary dendritic cells (DC) and regulatory T cells (TReg) play critical roles in mediating and maintaining such tolerance. In asthmatics, the same aeroallergens drive a maladaptive, Th2-biased immune response resulting in airway inflammation and airway hyper-reactivity. The mechanisms underlying the breakdown of inhalation tolerance, leading to the Th2-driven inflammation in rising numbers of asthmatic patients from industrialized countries remain elusive. The recent resurgence of interest in the role of the innate immune mediators in regulating adaptive immune response has sparked studies aimed at identifying the role of complement in allergic asthma. In this context, an unexpected role for the anaphylatoxin C5a receptor in allergic sensitization has been found. In models of experimental allergic asthma, ablation of C5aR signaling during initial allergen exposure either induced or enhanced Th2 sensitization. Mechanistically, C5aR signaling directly affected the function of distinct pulmonary DC subsets that induce or control allergen-induced adaptive immune responses. Signaling pathways downstream of C5 may also impact the function of TReg, as TReg from C5 sufficient, but not from C5 deficient mice, suppress DC activation and subsequent development of Th2-driven inflammation. The emerging paradigm is that constitutive local generation of C5a and C5aR signaling in airway DCs controls inhalation tolerance directly as well as indirectly through sensitization of airway DCs for TReg-mediated immunosuppression.
Journal: Molecular Immunology - Volume 44, Issues 1–3, January 2007, Pages 44–56