Effects of Lymphotoxin β Receptor Blockade on Intestinal Mucosal Immunity

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 β receptor blockade (LTβR) in PPs and intestine, and that stimulation with LTβR agonist antibodies reverses these defects. To confirm that LTβR regulates transcription of MAdCAM-1 message and more fully understand the effects of LTβR on MAdCAM-1 function within the mucosal immune system, we studied the effect of LTβR blockade with a chimeric LTβR 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 + LTβR-Ig fusion protein (100 μg IV), or PN + control Ig. The PPs of h...