TSLP promotes influenza-specific CD8+ T-cell responses by augmenting local inflammatory dendritic cell function

Mucosal Immunol. 2013 Jan;6(1):83-92. doi: 10.1038/mi.2012.50. Epub 2012 Jul 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens / immunology
  • Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Survival
  • Cytokines / metabolism*
  • Dendritic Cells / immunology*
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Influenza A virus / immunology*
  • Lung / immunology
  • Lung / metabolism
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Models, Immunological
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Thymic Stromal Lymphopoietin

Substances

  • Antigens
  • Cytokines
  • Thymic Stromal Lymphopoietin