title: B cells that produce immunoglobulin E mediate colitis in BALB/c mice.
abstract: OBJECTIVE
  Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Rα on T and B cells determines their effector functions and mediates oxazolone-induced colitis.
  
  
  METHODS
  We studied induction of colitis with oxazolone in wild-type mice and those with CD4(+) T cells that did not express IL-4Rα (Lck(cre)IL-4Rα(-/lox)). We also generated mice with B cells that did not express IL-4Rα (mb1(cre)IL-4Rα(-/lox)) and studied induction of colitis.
  
  
  RESULTS
  Lck(cre)IL-4Rα(-/lox) mice did not develop colitis in response to oxazolone, and their levels of IL-4, IL-13, and immunoglobulin (Ig) E were reduced. Adoptive transfer of naïve, wild-type CD4(+) Th cells depleted of natural killer T cells to Lck(cre)IL-4Rα(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-4Rα(-/lox) mice maintained their protection against colitis when IL-13-deficient CD4(+) T cells were transferred. These findings indicate that development of colitis involves not only natural killer T-cell functions, but also requires IL-13 production by CD4(+) T helper cells. Mb1(cre)IL-4Rα(-/lox) mice, which cannot produce IgE, were also protected against oxazolone-induced colitis. Blocking IgE binding significantly reduced mast cell numbers in colons and protected wild-type BALB/c mice from the onset of colitis.
  
  
  CONCLUSIONS
  IL-4 appears to induce CD4(+) Th2 cells to produce IL-13 and B cells to produce IgE, which together mediate oxazolone-induced colitis in mice.
authors: International Centre for Genetic Engineering and Biotechnology and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Jennifer C
authors: JC
authors: Hoving
authors: Frank
authors: F
authors: Kirstein
authors: Natalie E
authors: NE
authors: Nieuwenhuizen
authors: Lizette C E
authors: LC
authors: Fick
authors: Elias
authors: E
authors: Hobeika
authors: Michael
authors: M
authors: Reth
authors: Frank
authors: F
authors: Brombacher
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D007073:Immunoglobulin E / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D010081:Oxazolone; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation; D013997:Time Factors; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D057134:Antibodies, Neutralizing; D007073:Immunoglobulin E; D018793:Interleukin-13; D015847:Interleukin-4; D010081:Oxazolone; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit