Basic–alimentary tractMonoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice
Section snippets
Mice
C3H/HeJBir, C3H/HeJ, and C3H/HeSnJ-Pkrdcscid/Pkrdcscid (C3H.SCID) mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and housed in the University of Alabama animal facility. All studies were approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham.
Reagents and Materials
Reagents and materials were purchased from the following sources. RPMI 1640, fetal calf serum, 2-mercaptoethanol, HEPES, l-glutamine, and sodium pyruvate were purchased from Life Technologies
Enhanced Expression of IL-12, IL-23, and Related Cytokines in Inflamed Colon
To address the potential role of IL-23 and related cytokines in the induction of colitis by CBA-specific CD4+ T cells, we studied the expression of multiple genes in colonic tissues of recipient C3H.SCID mice using real-time quantitative PCR. A total of 1 × 106 cells of the Bir14 CBA-specific CD4+ T-cell line were adoptively transferred into C3H.SCID mice. Anti-CD3 polyclonally activated CD4+ T cells were transferred into a group of C3H.SCID mice as a negative control. Eight weeks after
Discussion
IL-23 is a member of a family of heterodimeric cytokines that includes IL-12 and IL-27. Both IL-12 and IL-23 are produced by dendritic cells and share the IL-12 p40 subunit. Both cytokines likely play a role in host defense at mucosal surfaces, but their exact role is unknown. Uptake of translocated commensal bacteria by murine intestinal dendritic cells increases the expression of IL-23 but not IL-12p70.21 The function of such IL-23–producing dendritic cells in normal immune homeostasis is
References (42)
- et al.
Spontaneous, heritable colitis in a new substrain of C3H/HeJ mice
Gastroenterology
(1994) - et al.
Cdcs1, a major colitogenic locus in mice, regulates innate and adaptive immune response to enteric bacterial antigens
Gastroenterology
(2005) - et al.
CD45RBhigh CD4+ T cells from IFN-gamma knockout mice do not induce wasting disease
J Autoimmun
(1997) - et al.
Understanding the IL-23-IL-17 immune pathway
Trends Immunol
(2006) - et al.
Interleukin-17 family members and inflammation
Immunity
(2004) - et al.
Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17
Immunity
(2005) - et al.
TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
Immunity
(2006) - et al.
Distinct inflammatory mechanisms mediate early versus late colitis in mice
Gastroenterology
(2002) - et al.
Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology
Immunity
(2006) - et al.
Th17: an effector CD4 T cell lineage with regulatory T cell ties
Immunity
(2006)
Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota
Immunol Rev
Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis
Am J Physiol
Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora
J Immunol
Colitis induced by enteric bacterial antigen-specific CD4+ T cells requires CD40-CD40 ligand interactions for a sustained increase in mucosal IL-12
J Immunol
Anti-interleukin-12 antibody for active Crohn’s disease
N Engl J Med
IL-12, but not IFN-gamma, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice
J Immunol
Studies with IL-10-/- mice: an overview
J Leukoc Biol
T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells
J Exp Med
In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts
Clin Exp Immunol
IL-12 and IL-23: master regulators of innate and adaptive immunity
Immunol Rev
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
J Exp Med
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Supported by grants PO1 DK044240, PO1 DK071176, and DK064400 from the National Institutes of Health.
- 1
C.O.E., Y.C., C.T.W., and T.R.S. have no conflict of interest to disclose.
- 2
T.K.M., R.B.F., and R.A.K. are employed by Schering-Plough Biopharma.