title: The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.
abstract: BACKGROUND
  Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses.
  
  
  RESULTS
  When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life.
  
  
  CONCLUSIONS
  We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Barberi
authors.forename: Alexis
authors.initials: A
authors.lastname: Dunkle
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
authors.forename: Luigi
authors.initials: L
authors.lastname: Racioppi
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Means
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D016827:CD8 Antigens; D008070:Lipopolysaccharides; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse