title: p8 Deficiency causes siderosis in spleens and lymphocyte apoptosis in acute pancreatitis.
abstract: OBJECTIVE
  The gene p8 was initially described in pancreatic tissue during acute experimental pancreatitis, a disease that is characterized by a systemic immune response. Although early reports suggested that p8 affects leukocyte migration during acute pancreatitis (AP), no studies revealing its immune-modulatory effects have been performed.
  
  
  METHODS
  We investigated the composition of the cellular immune system in naive p8 knockout (p8(−/−)) mice and compared with matched wild-type mice during pancreatitis.
  
  
  RESULTS
  In young mice, there were no relevant differences in the composition of peripheral and splenic CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD11b(+)Gr-1(-), and Gr-1 cells. In mature p8(−/−) mice, increased splenic CD4CD25FoxP3 cells, spleen siderosis, and increased marginal zones in the splenic white pulp were found. During AP, peripheral and splenic CD3(+) and CD3CD4 declined stronger in the p8(−/−) mice. The spleen of the p8(−/−) mice showed severe hypoplasia of the white pulp and mild hyperplasia of the red pulp. This was associated with a significantly increased rate of apoptosis.
  
  
  CONCLUSIONS
  We conclude that p8 has no impact on the cellular composition of the adaptive and innate immune systems in noninflammatory conditions. However, it may limit apoptosis and maintain homeostasis of the immune reaction during AP.
authors.affiliation: From the *Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology, and Dermatology, Universitätsklinikum Leipzig AöR, Leipzig; †Institute of Anatomy, Martin-Luther-Universität Halle-Wittenberg AöR, Halle/Saale; ‡Institute of Anatomy, Universität Leipzig, Leipzig, Germany; §Instituto Gulbenkian de Ciência, Oeiras, Portugal; ∥Fraunhofer Institute for Cell Therapy and Immunology; ¶Institute of Clinical Immunology, Universitätsklinikum Leipzig; #Translational Center for Regenerative Medicine, Universität Leipzig; and **Division of Hematology and Oncology, Department of Internal Medicine, Neurology, and Dermatology, Universitätsklinikum Leipzig AöR, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weis
authors.forename: Tilmann Cornelius
authors.initials: TC
authors.lastname: Schlaich
authors.forename: Faramarz
authors.initials: F
authors.lastname: Dehghani
authors.forename: Tânia
authors.initials: T
authors.lastname: Carvalho
authors.forename: Ines
authors.initials: I
authors.lastname: Sommerer
authors.forename: Stephan
authors.initials: S
authors.lastname: Fricke
authors.forename: Franka
authors.initials: F
authors.lastname: Kahlenberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Albrecht
authors.initials: A
authors.lastname: Hoffmeister
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002108:Ceruletide / Q000633:toxicity; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D006486:Hemosiderosis / Q000235:genetics*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009928:Organ Specificity; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013158:Splenic Diseases / Q000235:genetics*; D013163:Splenomegaly / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse; D002108:Ceruletide