Recent progress in understanding the interaction between immune/inflammatory cell subsets via interleukins, particularly reciprocal regulation and counter balance between Th1, Th2, Th9, Th17, Th22 and T regulatory cells, as well as B-cell subsets, bring new possibilities for immune intervention. With regard to allergic diseases, the process of developing selleck chemical such diseases is characterized by effector Th2 cells that produce IL-4, IL-5, IL-9 and IL-13 1–4. In addition, recently defined cytokines, such as IL-25, IL-31, IL-32 and IL-33 that contribute to Th2

responses, tissue inflammation, allergen-specific IgE production, eosinophilia, mucous production, and the activation and cell death of the epithelium represent newly emerging and essential players in the pathgogenesis of allergic inflammatory disease 5–9. In the context of tissue-related allergy-driving factors, the IL-1 family member cytokine IL-33 is becoming a key player in the initiation and exacerbation of inflammatory responses. Its effects are exerted via its heterodimeric receptor that consists of ST2 and the ubiquitously expressed IL-1 receptor accessory protein (ILRAcP) Natural Product Library clinical trial 10. IL-33 integrates both innate and adaptive immunity in a unique manner. It affects basophils, mast cells, eosinophils, innate lymphoid cells, NK and NKT cells and Th2 lymphocytes 2, 11. In addition, IL-33 impacts CD34pos precursor cell populations 12 and is involved

in the activation of a cell subpopulation called nuocytes that are crucial for Idelalisib manufacturer parasite repulsion. This nuocyte population was defined as lineageneg ICOSpos ST2pos IL-17RBpos and IL17Rapos

cells and is considered to be an upstream Th2 inducer/amplifier, whose properties still remain to be defined in detail 7. The actions of IL-33 seem to be particularly evident when looking at models of mucosal inflammation. In this issue of the European Journal of Immunology, an article by Besnard et al. adds significant information regarding the role of IL-33 in the context of a mouse model of asthma-like lung inflammation 13. The authors demonstrate that IL-33 acts, in an ST2-dependent manner, as a maturation factor for BM-derived DCs via up-regulation of CD80, CD40 and OX40L. This process is accompanied by the release of pro-inflammatory cytokines, such as IL-6, IL-1β, TNF-α and TARC/CCL17. IL-33-pre-treated DCs were significantly more potent than non-treated DCs at inducing allergen-specific proliferation in naïve T-cells, and the generated T-cell responses were of a Th2 type with IL-5 and IL-13 production. This activation/maturation of lung resident DCs was also confirmed in vivo via local application of IL-33, inducing up-regulation of the homing receptor CCR7 in the CD11cpos fraction. The activated DC phenotype was observed in the draining LN, and PBMCs from the LN displayed a Th2 phenotype upon re-stimulation with anti-CD3/CD28.