Τίτλος:
Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-β and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4 + T cells impaired Oas1g mRNA downstream of Ifnβ, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4 + T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.
Συγγραφείς:
Graser, A.
Ekici, A.B.
Sopel, N.
Melichar, V.O.
Zimmermann, T.
Papadopoulos, N.G.
Taka, S.
Ferrazzi, F.
Vuorinen, T.
Finotto, S.
Περιοδικό:
Mucosal Immunology
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
2',5' oligoadenylate synthetase; 2',5' oligoadenylate synthetase 1; beta interferon; interleukin 17; messenger RNA; transcription factor T bet; unclassified drug; 2',5' oligoadenylate synthetase; beta interferon; IL17A protein, human; interleukin 17; messenger RNA; OAS1 protein, human; ovalbumin; T box transcription factor; T-box transcription factor TBX21, A549 cell line; allergic asthma; animal cell; animal experiment; animal model; Article; CD4+ T lymphocyte; child; clinical article; controlled study; cytokine production; down regulation; female; gene expression; human; human cell; immune response; male; mouse; nonhuman; peripheral blood mononuclear cell; priority journal; Rhinovirus infection; Th17 cell; upper respiratory tract infection; viral clearance; A-549 cell line; animal; asthma; clinical trial; drug hypersensitivity; gene expression regulation; genetics; growth, development and aging; immunology; knockout mouse; lung; picornavirus infection; preschool child; primary cell culture; Rhinovirus; signal transduction; virology, 2',5'-Oligoadenylate Synthetase; A549 Cells; Animals; Asthma; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Drug Hypersensitivity; Female; Gene Expression Regulation; Humans; Interferon-beta; Interleukin-17; Lung; Male; Mice; Mice, Knockout; Ovalbumin; Picornaviridae Infections; Primary Cell Culture; Rhinovirus; RNA, Messenger; Signal Transduction; T-Box Domain Proteins
