Systemically circulating colitogenic memory CD4+T cells may be an ideal target for the treatment of inflammatory bowel diseases.
Inflammatory bowel diseases (IBD) are thought to be caused by a complex interaction of genetic, immunological, and environmental factors. Why is it that once an IBD develops it lasts a long time? Considering this simple question, we propose that coliotogenic memory CD4+T cells that remember the prototype of the disease in each patient are formed in IBD at the onset, and, perceiving them as "benign T-cell leukemia"-like lifelong memory CD4+T cells that hematogenously spread throughout the body, we thus propose that systemic circulating colitogenic memory CD4+T cells would be an ideal target for the treatment of IBD. Accordingly, selective depletion of colitogenic memory CD4+T cells by leukocytapheresis and blockade of circulation of colitogenic memory CD4+T cells by a newly developed immunosuppressant, FTY720, may be associated with dramatic efficacy and a marked reduction of inflammatory cytokines produced by activated leucocytes. We here describe the immunological pathogenesis focusing on the generation of circulating colitogenic memory CD4+T cells and the possible logics of leukocytapheresis and FTY720 for the treatment of IBD.
Kanai
Takanori
T
Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjyuku, Tokyo, Japan. takagast@sc.itc.keio.ac.jp
Watanabe
Mamoru
M
Hibi
Toshifumi
T
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003106:Colon / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology*; D007937:Leukapheresis; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine