Opposing Roles for Osteopontin DOI: 10.1038/Nri2109 an Intriguing Feature of Cytokines Is Established Mouse Model of Ovalbu- Restored OVA-Driven Responses, Indi

RESEARCH HIGHLIGHTS

ASTHMA AND ALLERGY Opposing roles for osteopontin DOI: 10.1038/nri2109 An intriguing feature of cytokines is established mouse model of ovalbu- restored OVA-driven responses, indi-

that depending on the time and the min (OVA)-induced allergic airway cating that the decrease in TH2-cell place, the same cytokine can have inflammation. In this model, priming observed after osteopontin opposite effects. A recent study in airway inflammation is induced by blockade was mediated by increased Nature Medicine describes how the sensitization with OVA plus alum numbers of pDCs that have a regula- cytokine osteopontin can have a followed by airway challenges with tory function. Conversely, during pro-inflammatory and detrimental OVA. The authors show that if mice secondary challenge, osteopontin effect during the primary phase of were given a neutralizing antibody blockade caused a more marked allergic airway disease but an anti- specific for osteopontin before the increase in the recruitment of inflammatory and protective effect sensitization phase, the inflamma- conventional DCs than pDCs to the during secondary antigenic chal- tory response to subsequent OVA draining lymph nodes. In co-cultures, lenge. These opposing effects of challenges was significantly dimin- conventional DCs from these drain- osteopontin in allergic disease seem ished compared with control mice. ing lymph nodes promoted the to be a result of its influence on the Thus, the antibody-treated mice differentiation of OVA-specific CD4+

recruitment of different subsets of showed decreased airway hyper- T cells into TH2 cells. So, the increased dendritic cells (DCs). responsiveness (AHR), a reduced recruitment of immunogenic conven- To assess the role of osteopontin inflammatory-cell infiltrate (includ- tional DCs provides an explanation

in the regulation of T helper 2 ing TH2 cells) in the lung-draining for the enhanced TH2-cell responses

(TH2)-cell-mediated allergic lymph nodes and lower levels of observed after osteopontin blockade

responses, Xanthou et al. used an TH2-cell-associated cytokines, such at the secondary challenge. as interleukin-4 (IL-4) and IL-13, in Finally, the authors tested the lymph-node cultures. By contrast, therapeutic potential of recombinant if osteopontin-specific neutralizing osteopontin in allergic disease. antibody was administered to mice Consistent with their previous immediately before secondary chal- observations, administration of lenge with OVA, the opposite effect recombinant osteopontin during was observed — AHR worsened, sensitization had a pro-inflammatory the inflammatory-cell infiltrate effect, whereas osteopontin admin-

increased and the levels of TH2-type istration during the secondary chal- cytokines were higher. So, neutrali- lenge decreased the inflammatory zation of osteopontin seems to have response and conferred protection different effects depending on the from allergic disease. stage of the allergic response. As dysregulated osteopontin How might this dichotomy be expression has been linked to achieved? Plasmacytoid DCs (pDCs) several autoimmune and cardio- have been shown to have a suppressive vascular diseases, osteopontin

effect on TH2-cell responses, so the might be of therapeutic benefit authors tested whether osteopontin in other disorders, if given at the blockade at the sensitization phase right stage. might affect pDC recruitment. Lucy Bird Indeed, compared with control mice, mice treated with osteopontin-specific ORIGINAL RESEARCH PAPER Xanthou, G. et al. antibody before sensitization showed Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell increased numbers of pDCs in the subsets. Nature Med. 13, 570–578 (2007) draining lymph nodes. Importantly, FURTHER READING Shinohara, M. L. & Cantor, H. the depletion of pDCs before sen- The bridge between dendritic cells and asthma. Nature Med. 13, 536–538 (2007) sitization and antibody treatment