TPI ASM8 attenuates the allergen-induced increase in target gene mRNA and airway responses in subjects with mild asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00264966).

SUMMARYThere is increasing evidence that primitive progenitors migrate from the bone marrow (BM) via the peripheral circulation to tissue sites where they undergo in situ differentiation to provide a continued source of effector cells, such as eosinophils, during an allergic in¯ammatory response. To study mechanisms of progenitor cell mobilization in allergic reactions, we investigated uctuations in the expression of the eotaxin receptor, CC chemokine receptor 3 (CCR3), on CD34 cells from stable asthmatics following allergen (i.e. antigen) challenge. BM aspirates were taken from seven early responder (ER) and 10 dual responder (DR) asthmatics who, following antigen challenge developed only an early bronchoconstrictor response and an early and latebronchoconstrictor response, respectively. Expression of CCR3 was detected on primitive (CD34 cells) and eosinophil-lineage committed progenitors (CD34 interleukin-5 receptor alpha-subunit cells) by¯ow cytometry and con®rmed by co-localization of CCR3 messenger RNA to CD34 immunopositive cells using in situ hybridization. When preantigen levels were compared to 24-hr postantigen levels, signi®cant increases in BM CD34 CCR3 cells were detected in DR, who also developed a signi®cant sputum and blood eosinophilia and increased methacholine airway responsiveness. In contrast, a signi®cant attenuation of BM CD34 CCR3 cells was observed in ER. In a dose-dependent manner eotaxin, but not interleukin (IL)-5, stimulated CD34 progenitor cell migration in vitro. This migrational response to eotaxin was abrogated by anti-CCR3 monoclonal antibody and primed by preincubation with IL-5. We propose that¯uctuations in CCR3 expression on human BM CD34 cells may facilitate chemokine-mediated progenitor cell mobilization to the peripheral circulation and the resultant development of pulmonary eosinophilia, a cardinal feature of asthma.

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IL-17RB is up-regulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.

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