MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis.

Background: Gut commensal microbes affect the development and activation of the mucosal and systemic immune systems. However, the exact molecular mechanism of these microbes that is involved in the development of colitis remains unclear.

Methods: The present study was conducted to determine the distinct role of the innate immune system in the development of a dextran sulfate sodium (DSS) colitis model in MyD88(-/-) mice, because myeloid differentiation protein (MyD88) is a major adaptor molecule essential for signaling via Toll-like receptors (TLRs).

Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.

Several studies indicate that CD4(+) T cells, macrophages, and dendritic cells initially mediate intestinal inflammation in murine models of human inflammatory bowel disease. However, the initial role of B cells in the development of intestinal inflammation remains unclear. In this study we present evidence that B cells can trigger intestinal inflammation using transgenic (Tg) mice expressing CD40 ligand (CD40L) ectopically on B cells (CD40L/B Tg).

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice.

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed.

The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocecitis.

Lympho-haemopoietic progenitors residing in murine gut cryptopatches (CPs) have been shown to generate intestinal extrathymic intraepithelial lymphocytes (IELs). However, the role of CPs in the development of intestinal inflammation remains unclear. To investigate the role of CPs in the development of intestinal inflammation, we examined SAMP1/Yit mice, which spontaneously develop a chronic intestinal inflammation localized to the terminal ileum and cecum.

Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis.

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea.