Prenatal blockage of lymphotoxin beta receptor and TNF receptor p55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine.
Signaling by lymphotoxin (LT) and TNF is essential for the organogenesis of secondary lymphoid tissues in systemic and mucosal compartments. In this study, we demonstrated that the progeny of mice treated with fusion protein of LTbetaR and IgGFc (LTbetaR-Ig) or LTbetaR-Ig plus TNFR55-Ig (double Ig) showed significantly increased numbers of isolated lymphoid follicles (ILF) in the large intestine. Interestingly, double Ig treatment accelerated the maturation of large intestinal ILF. Three-week-old progeny of double Ig-treated mice showed increased numbers of ILF in the large intestine, but not in the small intestine. Furthermore, alteration of intestinal microflora by feeding of antibiotic water did not affect the increased numbers of ILF in the large intestine of double Ig-treated mice. Most interestingly, mice that developed numerous ILF also had increased levels of activation-induced cytidine deaminase expression and numbers of IgA-expressing cells in the lamina propria of the large intestine. Taken together, these results suggest that ILF formation in the large intestine is accelerated by blockage of LTbetaR and TNFR55 signals in utero, and ILF, like colonic patches, might play a role in the induction of IgA response in the large intestine.
Kweon
Mi-Na
MN
Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Korea. mnkweon@ivi.int
Yamamoto
Masafumi
M
Rennert
Paul D
PD
Park
Eun Jeong
EJ
Lee
Ah-Young
AY
Chang
Sun-Young
SY
Hiroi
Takachika
T
Nanno
Masanobu
M
Kiyono
Hiroshi
H
D000818:Animals; D049109:Cell Proliferation; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007420:Intestine, Large / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D007070:Immunoglobulin A; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I