title: Effects of lymphotoxin beta receptor blockade on intestinal mucosal immunity.
abstract: BACKGROUND
  Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) directs lymphocyte migration into gut-associated lymphoid tissue (GALT) through Peyer's patches (PPs). Parenteral nutrition (PN) impairs mucosal immunity by reducing PPs MAdCAM-1 expression, T and B cells in GALT, and intestinal and respiratory immunoglobulin (Ig) A levels. We previously showed that PN reduces lymphotoxin beta receptor blockade (LTbetaR) in PPs and intestine, and that stimulation with LTbetaR agonist antibodies reverses these defects. To confirm that LTbetaR regulates transcription of MAdCAM-1 message and more fully understand the effects of LTbetaR on MAdCAM-1 function within the mucosal immune system, we studied the effect of LTbetaR blockade with a chimeric LTbetaR Ig-fusion protein on MAdCAM-1 mRNA levels, PP lymphocyte mass and IgA levels in the intestinal and respiratory tracts.
  
  
  METHODS
  Mice were cannulated and killed 3 days after receiving chow + control Ig, chow + LTbetaR-Ig fusion protein (100 microg IV), or PN + control Ig. The PPs of half of the animals were processed for lymphocyte count, and the other half were processed for complementary DNA and subsequent polymerase chain reaction (PCR). mRNA levels of MAdCAM-1 were determined by real-time PCR; intestinal and respiratory IgA levels were measured by ELISA.
  
  
  RESULTS
  PN significantly reduced PP lymphocyte mass, MAdCAM-1 mRNA, and intestinal IgA. As anticipated, LTbetaR blockade significantly decreased PP cells and MAdCAM-1 mRNA, but not intestinal IgA because chow feeding was maintained. Both LTbetaR blockade and PN decreased nasal IgA, but not significantly.
  
  
  CONCLUSIONS
  LTbetaR blockade in chow animals significantly reduces transcription of MAdCAM-1 gene and PPs lymphocyte mass. These data implicate inadequate LTbetaR signaling as a major mechanism for decreased GALT cells with lack of enteral stimulation, and further establish the role of LTbetaR in the mucosal immune system.
authors: Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, Madison, Wisconsin, USA.
authors: Woodae
authors: W
authors: Kang
authors: Kenneth A
authors: KA
authors: Kudsk
authors: Yoshifumi
authors: Y
authors: Sano
authors: Jinggang
authors: J
authors: Lan
authors: Fu
authors: F
authors: Yang-Xin
authors: F Enrique
authors: FE
authors: Gomez
authors: Yoshinori
authors: Y
authors: Maeshima
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D007136:Immunoglobulins / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology; D018655:Lymphocyte Count; D053259:Lymphotoxin beta Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009088:Mucoproteins / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
chemical_list: D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007136:Immunoglobulins; D053259:Lymphotoxin beta Receptor; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D012333:RNA, Messenger