IL-6 in OSM-Driven Pulmonary Independently of IL-6, Despite a Role for (OSM) Promotes Inducible BALT Formation Pulmonary Expression of Oncostatin M

Inducible BALT (iBALT) is associated with immune responses to respiratory infections as well as with local pathology derived from chronic inflammatory lung diseases. In this study, we assessed the role of oncostatin M (OSM) in B cell activation and iBALT formation in mouse lungs. We found that C57BL/6 mice responded to an endotracheally administered adenovirus vector expressing mouse OSM, with marked iBALT formation, increased cytokine (IL-4, IL-5, IL-6, IL-10, TNF-a, and IL-12), and chemokine (CXCL13, CCL20, CCL21, eotaxin-2, KC, and MCP-1) production as well as inflammatory cell accumulation in the airways. B cells, T cells, and dendritic cells were also recruited to the lung, where many displayed an activated phenotype. Mice treated with control adenovirus vector (Addl70) were not affected. Interestingly, IL-6 was required for inflammatory responses in the airways and for the expression of most cytokines and chemokines. However, iBALT formation and lymphocyte recruitment to the lung tissue occurred independently of IL-6 and STAT6 as assessed in gene-deficient mice. Collectively, these results support the ability of OSM to induce B cell activation and iBALT formation independently of IL-6 and highlight a role for IL-6 downstream of OSM in the induction of pulmonary inflammation. T he gp130 family of cytokines, including IL-6, IL-11, LIF, IL-31, and oncostatin M (OSM), plays various roles in inflammation, hematopoiesis, and immune responses (1, 2). Receptors for this family of cytokines share a common subunit, gp130, which complexes with a variety of cell surface and soluble receptor chains that provide specificity for the separate ligands (2). Functions of this family of cytokines in mucosal immunity are complex and overlapping due to the combinatorial expression of shared and specific receptor subunits on various cell types. Previous studies indicate shared but also private and sp. act. of OSM among gp130 cytokines (2, 3). However, the regulatory roles of OSM in lung mucosal immunity are currently unclear. OSM is a 26-kDa extracellular proinflammatory glycoprotein that promotes connective tissue remodeling, chemokine expression , and infiltration of inflammatory granulocytes, lymphocytes, and myeloid cells in animal models (4–8). Lung OSM levels are elevated in patients with severe asthma (9), allergic rhinitis (10), and idiopathic pulmonary fibrosis (IPF) (11). Inflammatory mono-nuclear cells are a major source of OSM (12), whereas its specific receptors, consisting of gp130 and an OSM-specific receptor-b subunit (3), are broadly expressed by structural cells, such as fibroblasts, osteoblasts, smooth muscle cells, and endothelial cells. Although the effects of …