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[CD4.sup.+] T-helper cells that selectively produce interleukin (IL)-17 ([T.sub.H]17), are critical for host defence and autoimmunity (1-4). Although crucial for [T.sub.H]17 cells in vivo (5,6), IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-[β.sub.1] have been proposed to be the factors responsible for initiating specification (7-10). Here we show that [T.sub.H]17 differentiation can occur in the absence of TGF-β signalling. Neither IL-6 nor IL-23 alone efficiently generated [T.sub.H]17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naive precursors, independently of TGF-β. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed RORγt (encoded by Rorc) and T-bet. [T-bet.sup.+] RORy[t.sup.+] [T.sub.H]17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred [T.sub.H]17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data indicate an alternative mode for [T.sub.H]17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications., TGF-βl is important for murine [T.sub.H]17 differentiation (7,8) and accordingly, transgenic expression of a mutant TGF-β subunit receptor II (CD4dnTGF-βRII) in T cells interferes with the generation of [T.sub.H]17 cells [...]

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Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins (1). It is induced in activated T cells and is reported to process a variety [...]

Surfactant protein-A (SP-A) plays multiple roles in pulmonary host defense, including stimulating bacterial phagocytosis by innate immune cells. Previously, SP-A was shown to interact with complement protein C1q. Our goal was to further characterize this interaction and elucidate its functional consequences. Radiolabeled SP-A bound solid-phase C1q but not other complement proteins tested. The lectin activity of SP-A was not required for binding to C1q. Because C1q is involved in bacterial clearance but alone does not efficiently enhance the phagocytosis of most bacteria, we hypothesize that SP-A enhances phagocytosis of C1q-coated antigens. SP-A enhanced by sixfold the percentage of rat alveolar macrophages in suspension that phagocytosed C1q-coated fluorescent beads. Furthermore, uptake of C1q-coated beads was enhanced when either beads or alveolar macrophages were preincubated with SP-A. In contrast, SPA had no significant effect on the uptake of C1q-coated beads by alveolar macrophages adhered to plastic slides. We conclude that SP-A may serve a protective role in the lung by interacting with C1q to enhance the clearance of foreign particles. lung; innate immunity; complement; collectins

Interleukin-22, a component of the immune system most studied for its role in autoimmunity, has a more beneficial side. Two studies show how this cytokine fights off microbes in the [...]

Watford, Wendy T., Andrew J. Ghio, and Jo Rae Wright. Complement-mediated host defense in the lung. Am J Physiol Lung Cell Mol Physiol 279: L790-L798, 2000.--Complement is a system of plasma proteins that aids in the elimination of pathogens from the body. We hypothesized that there is a functional complement system present in the lung that aids in the removal of pathogens. Western blot analysis revealed complement proteins of the alternative and classical pathways of complement in bronchoalveolar lavage fluids (BALF) from healthy volunteers. Functional classical pathway activity was detected in human BALF, but there was no significant alternative pathway activity in lavage fluid, a finding that correlates with the low level of the alternative pathway protein, factor B, in these samples. Although the classical pathway of complement was functional in lavage fluid, the level of the classical pathway activator C1q was very low. We tested the ability of the lung-specific surfactant proteins, surfactant protein A (SP-A) and surfactant protein D (SP-D), to substitute for C1q in classical pathway activation, since they have structural homology to C1q. However, neither SP-A nor SP-D restored classical pathway activity to C1q-depleted serum. These data suggest that the classical pathway of complement is functionally active in the lung where it may play a role in the recognition and clearance of bacteria. bronchoalveolar lavage fluid; surfactant protein A; C1q; collectin