Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis.
BACKGROUND
Inflammatory bowel disease (IBD) affects approximately 4 million people worldwide and can be caused by dysregulated mucosal immune responses to the intestinal commensal microflora. Immunoglobulin A (IgA) is considered to be the principal antibody in intestinal secretions and functions to prevent commensals and pathogenic organisms from gaining access to epithelial cell surfaces. Immunoglobulin A deficiency in humans has been associated with celiac disease and ulcerative colitis. However, the precise role of IgA in the pathogenesis of these disorders is yet to be fully understood.


METHODS
Mice with a targeted disruption in IgA production (IgA(-/-) mice) and polymeric immunoglobulin receptor (pIgR(-/-) mice) were analyzed for the contribution of secretory immunity in the pathogenesis of dextran sulfate sodium (2.5%)-induced colitis.


RESULTS
It was found that dextran sulfate sodium-treated pIgR(-/-) mice displayed greater loss of bodyweight and had severe clinical illness compared to similarly treated IgA(-/-) mice and wild-type animals. Additionally, colonic tissues from the pIgR(-/-) mice exhibited progressively and significantly greater degrees of mucosal edema, ulceration, crypt abscesses and macrophage infiltration when compared to similarly treated IgA(-/-) mice and wild-type animals.


CONCLUSIONS
The results indicate that secretory immunoglobulins contribute to protection of the colonic mucosa against dextran sulfate sodium-induced epithelial injury, although the isotype of the secretory immunoglobulin (IgA or IgM) may not be a decisive factor in such protection. Collectively, the pIgR and/or the secretory component are important for the maintenance of epithelial integrity and mucosal homeostasis in the colonic epithelium.
Murthy
Ashlesh K
AK
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA.
Dubose
Candice N
CN
Banas
Jeffrey A
JA
Coalson
Jacqueline J
JJ
Arulanandam
Bernard P
BP
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D016264:Dextran Sulfate; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009780:Occult Blood; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics / Q000276:immunology*
D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D016264:Dextran Sulfate