TSLP promotes influenza-specific CD8+ T-cell responses by augmenting local inflammatory dendritic cell function.
Thymic stromal lymphopoietin (TSLP) is a mucosal tissue-associated cytokine that has been widely studied in the context of T helper type 2 (Th2)-driven inflammatory disorders. Although TSLP is also produced upon viral infection in vitro, the role of TSLP in antiviral immunity is unknown. In this study we report a novel role for TSLP in promoting viral clearance and virus-specific CD8+ T-cell responses during influenza A infection. Comparing the immune responses of wild-type and TSLP receptor (TSLPR)-deficient mice, we show that TSLP was required for the expansion and activation of virus-specific effector CD8+ T cells in the lung, but not the lymph node. The mechanism involved TSLPR signaling on newly recruited CD11b+ inflammatory dendritic cells (DCs) that acted to enhance interleukin-15 production and expression of the costimulatory molecule CD70. Taken together, these data highlight the pleiotropic activities of TSLP and provide evidence for its beneficial role in antiviral immunity.
Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, Lausanne, Switzerland.
K
K
Yadava
A
A
Sichelstiel
I F
IF
Luescher
L P
LP
Nicod
N L
NL
Harris
B J
BJ
Marsland
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D000094632:Thymic Stromal Lymphopoietin
D000941:Antigens; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin