TLR-2 Activation Induces Regulatory T Cells and Long-Term Suppression of Asthma Manifestations in Mice

<p>Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction and airway hyperresponsiveness (AHR). The T regulatory (Treg) cell subset is critically important for the regulation of immune responses. Adoptive transfer of Treg cells has been shown to be sufficient for the suppression of airway inflammation in experimental allergic asthma. Intervention strategies aimed at expanding the Treg cell population locally in the airways of sensitized individuals are therefore of high interest as a potential therapeutic treatment for allergic airway disease. Here, we aim to test whether long-term suppression of asthma manifestations can be achieved by locally expanding the Treg cell subset via intranasal administration of a TLR-2 agonist. To model therapeutic intervention aimed at expanding the endogenous Treg population in a sensitized host, we challenged OVA-sensitized mice by OVA inhalation with concomitant intranasal instillation of the TLR-2 agonist Pam3Cys, followed by an additional series of OVA challenges. Pam3Cys treatment induced an acute but transient aggravation of asthma manifestations, followed by a reduction or loss of AHR to methacholine, depending on the time between Pam3Cys treatment and OVA challenges. In addition, Pam3Cys-treatment induced significant reductions of eosinophils and increased numbers of Treg cells in the lung infiltrates. Our data show that, despite having adverse acute effects, TLR2 agonist treatment as a therapeutic intervention induces an expansion of the Treg cell population in the lungs and results in long-term protection against manifestation of allergic asthma upon subsequent allergen provocation. Our data indicate that local expansion of Tregs in allergic airway disease is an interesting therapeutic approach that warrants further investigation.</p>

From Cancer Mimicking Orphan Lung Disease to Orphan Thoracic Oncology

International audienceA variety of rare neoplastic and non-neoplastic disorders may develop in the lung, the pleura, and the mediastinum. Some may have a propensity to mimic lung carcinoma as well as benign orphan lung diseases at some level of examination, as they may share with these clinical, imaging, pathological, and even molecular features. Challenges in the differential diagnoses among reciprocal mimics are well illustrated through examples as bronchioloalveolar carcinoma, primary pulmonary lymphomas, and vascular sarcomas. Pseudotumors have further been described, actually corresponding to a heterogeneous group of diseases characterised by circumscribed fibrous tissue and inflammatory cells. Among the inflammatory pseudotumors, neoplastic/non-neoplastic borderline disorders have been identified, such as inflammatory myofibroblastic tumor, which presents with clonal proliferation and has eventually emerged as a true neoplasm. Finally, some rare pulmonary diseases are emerging as borderline neoplastic non-neoplastic disorders, that require multidisciplinary expertise both in the field of orphan pulmonary diseases and in thoracic oncology, including amyloidosis or even Langerhans cell histiocytosis. Ultimately, implementing multi-disciplinary expert consensus is mandatory to determine the optimal management of these disorders