title: MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis.
abstract: 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). To this end, MyD88(-/-) and wild-type (WT) mice received sterile distilled water containing 1.2% DSS for 8 days. The survival rate, total clinical score (body weight loss, stool consistency, and rectal bleeding), colon length, and histological score were assessed. The expression of surface markers (F4/80 and CD4) on infiltrating lamina propria mononuclear cells was analyzed immunohistochemistrically.
  
  
  RESULTS
  MyD88(-/-) mice exhibited increased susceptibility to DSS-induced colitis, as reflected by significantly higher lethality and higher clinical and histological scores, and more severe colonic shortening compared to WT mice. Immunohistochemical analysis revealed a significant increase of both F4/80+ macrophages and CD4+ T cells in the inflamed mucosa in DSS-fed MyD88(-/-) mice compared to DSS-fed WT mice.
  
  
  CONCLUSIONS
  These findings suggest that, via MyD88 signaling, the innate immune system in the gut plays an important protective role in colitis.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Araki
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikura
authors.forename: Shin
authors.initials: S
authors.lastname: Makita
authors.forename: Koji
authors.initials: K
authors.lastname: Uraushihara
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Iiyama
authors.forename: Teruji
authors.initials: T
authors.lastname: Totsuka
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000187:drug effects*; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D000943:Antigens, Differentiation / Q000187:drug effects*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000378:metabolism; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000401:mortality; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000401:mortality; D053727:Interleukin-18 Receptor alpha Subunit; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000187:drug effects*; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism; D053724:Receptors, Interleukin-18; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D012720:Severity of Illness Index; D000099192:CD69 Antigens
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D016264:Dextran Sulfate; D053727:Interleukin-18 Receptor alpha Subunit; D037181:Lectins, C-Type; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C508573:Il18r1 protein, mouse; C507780:Myd88 protein, mouse