Environmental-mediated intestinal homeostasis in neonatal mice.
BACKGROUND
Immunoglobulin A (IgA) plays a key role in coating luminal antigens and preventing translocation of harmful bacteria. The aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor that when stimulated activates factors important for barrier function and intestinal homeostasis. We hypothesize that AhR signaling is critical for establishment of intestinal homeostasis in neonates.


METHODS
Mice: C57BL/6 (B6) AhR+/+ wild type (WT), B6.AhR-/- Aryl-hydrocarbon receptor knockout (KO), and B6.AhR+/+ raised on an AhR ligand-free diet (AhR LF). Enzyme-linked immunosorbent assay was used to measure fecal and serum IgA levels. Bacterial translocation was measured by culturing the mesenteric lymph nodes.


RESULTS
Two week old KO mice had significantly less fecal IgA compared with WT (and AhR LF, P value = 0.0393. The amount of IgA from the gastric contents of 2-wk-old mice was not significantly different. At age 8 wk, AhR LF mice had significantly less fecal IgA than WT and KO P value = 0.0077. At 2 wk, KO mice had significantly higher levels of bacterial translocation and at 8 wk AhR LF had significantly higher levels of bacterial translocation compared with WT.


CONCLUSIONS
In neonatal mice, the lack of AhR signaling is associated with loss of intestinal homeostasis, evidenced by decreased levels of IgA and increased bacterial translocation. In adult mice, exogenous AhR ligand and not receptor signaling is necessary for maintenance of intestinal integrity.
Department of Surgery, University of Alabama, Children's of Alabama, Birmingham, Alabama.
Courtney
C
Culbreath
Department of Biological, Earth, and Physical Sciences, Limestone College, Gaffney, South Carolina.
Scott M
SM
Tanner
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama.
Venkata A
VA
Yeramilli
Department of Surgery, University of Alabama, Children's of Alabama, Birmingham, Alabama.
Taylor F
TF
Berryhill
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
Robin G
RG
Lorenz
Department of Surgery, University of Alabama, Children's of Alabama, Birmingham, Alabama. Electronic address: colin.martin@childrensal.org.
Colin A
CA
Martin
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000502:physiology; D018988:Bacterial Translocation; D006706:Homeostasis; D007070:Immunoglobulin A / Q000097:blood; D007422:Intestines / Q000276:immunology*; D008214:Lymphocytes / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
D007070:Immunoglobulin A; D018336:Receptors, Aryl Hydrocarbon
B cells; Immunoglobulins; Intestinal homeostasis; Necrotizing enterocolitis