To cite this article: Kavanagh H, Mahon BP. Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 2011; 66: 523–531. Abstract Background:  Adult bone marrow‐derived mesenchymal stem cells (MSC) possess potent immune modulatory effects which support their possible use as a therapy for immune‐mediated disease. MSC induce regulatory T cells (Treg) in vitro although the in vivo relevance of this is not clear. Objective:  This study addressed the hypothesis that adult bone marrow derived‐MSC would prevent the pathology associated with allergen‐driven airway inflammation, and sought to define the effector mechanism. Methods:  The influence of allogeneic MSC was examined in a model system where Treg induction is essential to prevent pathology. This was tested using a combination of a model of ovalbumin‐driven inflammation with allogeneic MSC cell therapy. Results:  Systemic administration of allogeneic MSC protected the airways from allergen‐induced pathology, reducing airway inflammation and allergen‐specific IgE. MSC were not globally suppressive but induced CD4+FoxP3+ T cells and modulated cell‐mediated responses at a local and systemic level, decreasing IL‐4 but increasing IL‐10 in bronchial fluid and from allergen re‐stimulated splenocytes. Moderate dose cyclophosphamide protocols were used to differentially ablate Treg responses; under these conditions the major beneficial effect of MSC therapy was lost, suggesting induction of Treg as the key mechanism of action by MSC in this model. In spite of the elimination of Treg, a significant reduction in airway eosinophilia persisted in those treated with MSC. Conclusion:  These data demonstrate that MSC induce Tregin vivo and reduce allergen‐driven pathology. Multiple Treg dependent and independent mechanisms of therapeutic action are employed by MSC.

SummaryBackground Virulent Bordetella pertussis, the causative agent of whooping cough, exacerbates allergic airway inflammation in a murine model of ovalbumin (OVA) sensitization. A live genetically attenuated B. pertussis mucosal vaccine, BPZE1, has been developed that evokes full protection against virulent challenge in mice but the effect of this attenuated strain on the development of allergic responses is unknown. Objective To assess the influence of attenuated B. pertussis BPZE1 on OVA priming in a murine model of allergic airway inflammation. Methods Mice were challenged with virulent or attenuated strains of B. pertussis, and sensitized to allergen (OVA) at the peak of bacterial carriage. Subsequently, airway pathology, local inflammation and OVA-specific immunity were examined. Results In contrast to virulent B. pertussis, live BPZE1 did not exacerbate but reduced the airway pathology associated with allergen sensitization. BPZE1 immunization before allergen sensitization did not have an adjuvant effect on allergen specific IgE but resulted in a statistically significant decrease in airway inflammation in tissue and bronchoalveolar lavage fluid. BPZE1 significantly reduced the levels of OVA-driven IL-4, IL-5 and IL-13 but induced a significant increase in IFN-g in response to OVA re-stimulation. Conclusions These data demonstrate that, unlike virulent strains, the candidate attenuated B. pertussis vaccine BPZE1 does not exacerbate allergen-driven airway pathology. BPZE1 may represent an attractive T-helper type 1 promoting vaccine candidate for eradication of whooping cough that is unlikely to promote atopic disease.

Background aims: Next-generation immune cell therapy products will require complex modifications using engineering technologies that can maintain high levels of cell functionality. Non-viral engineering methods have the potential to address limitations associated with viral vectors. However, while electroporation is the most widely used non-viral modality, concerns about its effects on cell functionality have led to the exploration of alternative approaches. Here the authors have examined the suitability of the Solupore non-viral delivery system for engineering primary human T cells for cell therapy applications. Methods: The Solupore system was used to deliver messenger RNA (mRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) guide RNA ribonucleoprotein (RNP) cargos to T cells, and efficiency was measured by flow cytometry. Cell perturbation was assessed by immune gene expression profiling, including an electroporation comparator. In vitro and in vivo cytotoxicity of chimeric antigen receptor (CAR) T cells generated using the Solupore system was evaluated using a realtime cellular impedance assay and a Raji-luciferase mouse tumor model, respectively. Results: Efficient transfection was demonstrated through delivery of mRNA and CRISPR CAS9 RNP cargos individually, simultaneously and sequentially using the Solupore system while consistently maintaining high levels of cell viability. Gene expression profiling revealed minimal alteration in immune gene expression, demonstrating the low level of perturbation experienced by the cells during this transfection process. By contrast, electroporation resulted in substantial changes in immune gene expression in T cells. CAR T cells generated using the Solupore system exhibited efficient cytotoxicity against target cancer cells in vitro and in vivo. Conclusions: The Solupore system is a non-viral means of simply, rapidly and efficiently delivering cargos to primary human immune cells with retention of high cell viability and functionality.

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Nurses play an important role in the care of patients treated with radiotherapy (RT) for skin conditions, such as skin cancers. This is the final article in a four-part series that aims to supplement general oncology nurse training by providing a scientific basis to better understand a) the use of RT in skin and its diseases; and b) the management of acute skin RT reactions to achieve best patient outcomes. The first article focused on the role of the nurse within the radiation oncology department and the initial patient assessment. The second article revised the anatomy, physiology, pathologies and radiobiology of skin. The third described the skin RT prescription and plan, especially in relation to volume and dose. The aim of this fourth article is to assist the nurse, by applying the knowledge from the previous articles, to predict, explain and care for the acute side effects that may arise during a course of skin radiotherapy.

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