system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Colitis, Disease Models, Animal, Female, Immunity, Mucosal, Interleukin-12 Subunit p35, Interleukins, Intestinal Mucosa, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Minor Histocompatibility Antigens, Phenotype, Receptors, Cytokine, T-Lymphocytes, Th1 Cells, Th17 Cells, Up-Regulation.
user
Does interleukin-35 mediate mucosal immune responses that protect against T-cell-dependent colitis? Context: The soluble hematopoietin receptor Epstein-Barr virus-induced protein (EBI)-3 is an immune regulator that has been associated with the pathogenesis of inflammatory bowel disease. However, the concept that EBI3 is part of an interleukin (IL)-27 heterodimer that mediates chronic inflammatory and autoimmune diseases has been challenged by the description of IL-35, a bioactive cytokine comprising EBI3 and IL-12 p35. We investigated the roles of IL-27 and IL-35 in chronic inflammation of the intestine. We analyzed EBI3-deficient mice and IL-27p28-deficient mice with spontaneous or T-cell transfer-induced colitis and compared outcomes with wild-type mice (controls). We constructed vectors that express EBI3 covalently linked to the IL-12p35 chain (recombinant [r]IL-35). Intestines of EBI3-deficient mice had increased pathologic features of colitis, compared with IL-27p28-deficient or control mice; they also had shorter survival times, indicating that IL-35, rather than IL-27, protects the intestine from immune responses in mice. The mucosa of EBI3-deficient mice accumulated subsets of activated CD4+ T cells that produced T-helper (Th)1 and Th17 cytokines. Adoptive transfer of these T cells induced colitis in RAG-deficient mice. The rIL-35 significantly reduced the development of several forms of experimental colitis and reduced levels of markers of Th1 and Th17 cells.
assistant
IL-35 controls the development of T-cell-dependent colitis in mice. It might be developed as a therapeutic target for patients with chronic intestinal inflammation. Final Decision: yes