Role of PD-L1 and PD-L2 in allergic diseases and asthma - PubMed (original) (raw)

Review

Role of PD-L1 and PD-L2 in allergic diseases and asthma

A K Singh et al. Allergy. 2011 Feb.

Abstract

Asthma is the result of chronic airway inflammation associated predominantly with CD4+ cells, eosinophils, mast cells, and basophils. Several T-cells subsets, including NKT cells, play a critical role in orchestrating the inflammation in the airways predominantly, by secreting interleukin-4 and interleukin-13. Recently, programmed death-1 (PD-1) with its ligands, programmed death ligand B7H1 (PD-L1) and B7DC (PD-L2), was shown to regulate T-cell activation and tolerance. PD-1 has been characterized as a negative regulator of conventional CD4+T cells. In addition, the relative roles of PD-L1 and PD-L2 in regulating the activation and function of T cells have recently been characterized. Recent studies have demonstrated that PD-L1 and PD-L2 have important but opposing roles in modulating and polarizing T-cell functions in airway hyperreactivity. Whereas the severity of asthma is greatly enhanced in absence of PD-L2, PD-L1 deficiency resulted in reduced airway hyperresponsiveness and only minimal inflammation. This observation is partially because of the polarization of NKT cells in PD-L1- and PD-L2-deficient mice. This review will discuss the recent literature regarding the role of PD-L1 and PD-L2 in allergic disease and asthma. Current understanding of the role of PD ligands in allergic asthma gives impetus to the development of novel therapeutic approaches.

© 2010 John Wiley & Sons A/S.

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Figures

Figure 1

Figure 1. Role of programmed cell death ligands, PD-L1 and PD-L2 in allergic asthma

Upon recognition and activation, pulmonary dendritic cells express PD-L1 and PD-L2. PD-1/PD-L1 interaction produces a Th2 response with more IL-4 production which leads to increased AHR (right). However, PD-1/PD-L2 interaction initiates a Th1 type response with increased expression of IFN-γ and subsequently reduces the AHR (left). Simultaneous expression of PD-L1 and PD-L2 neutralizes the single effects and does not lead to immediate polarization of T cells (middle).

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