title: Parenteral nutrition impairs gut-associated lymphoid tissue and mucosal immunity by reducing lymphotoxin Beta receptor expression.
abstract: OBJECTIVE
  To determine the effects of parenteral nutrition (PN) on LTbetaR in gut-associated lymphoid tissue (GALT), particularly the intestine and Peyer's patches (PP).
  
  
  BACKGROUND
  Lack of enteral stimulation with PN impairs mucosal immunity and reduces IgA levels through depression of GALT cytokines (IL-4 and IL-10) and GALT specific adhesion molecules. We have shown that each is critical to intact mucosal immunity through effects on lymphocyte homing, IgA production, and resistance to antibacterial and antiviral immunity. IgA is the principal specific immunologic mucosal defense. LTbetaR stimulation controls production of IL-4, the adhesion molecule MAdCAM-1, and other key components of GALT, all of which are important in increasing IgA levels and maintaining mucosal defenses.
  
  
  METHODS
  Experiment 1: LTbetaR expression in intestine and PP was analyzed by Western blot after 5 days of chow, a complex enteral diet (CED), or PN. Diets were isocaloric and isonitrogenous except for chow. Experiment 2: After completing pilot experiments to determine the appropriate dose of the LTbetaR agonistic antibody, mice received chow, PN + 5 mug of anti-LTbetaR mAb (2 times/d, i.v.) or PN + isotype control antibody. PP lymphocytes and intestinal IgA levels were measured after 2 days.
  
  
  RESULTS
  Lack of enteral stimulation with PN significantly decreased LTbetaR expression in intestine and PP compared with chow and CED. LTbetaR stimulation with an agonistic anti-LTbetaR mAb significantly increased PP lymphocyte counts and intestinal IgA in PN fed-mice.
  
  
  CONCLUSIONS
  LTbetaR expression is critical for GALT control mechanisms and intact mucosal immunity. PN reduces LTbetaR expression, PP lymphocytes, and intestinal IgA production. Exogenous LTbetaR stimulation reverses PN-induced depression of gut mucosal immunity.
authors.affiliation: Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, Madison, WI, USA.
authors.forename: Woodae
authors.initials: W
authors.lastname: Kang
authors.forename: F Enrique
authors.initials: FE
authors.lastname: Gomez
authors.forename: Jinggang
authors.initials: J
authors.lastname: Lan
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sano
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueno
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D018928:Immunity, Mucosal / Q000502:physiology*; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D007421:Intestine, Small; D018655:Lymphocyte Count; D053259:Lymphotoxin beta Receptor; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010288:Parenteral Nutrition; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor