Galectin-9-secreting cell, and production method and use of the same

Abstract

The object of the present invention is to provide a cell that can exhibit physiological activity based on galectin-9, a method for producing the cell, and use of the cell. In order to achieve the above object, the cell of the present invention contains galectin-9, and the galectin-9 is expressed on a cell surface.

1 . A cell not comprising DNA coding for galectin-9 having a signal peptide, wherein
 the cell has an ability to secrete galectin-9 and expresses the galectin 9 on a cell surface.   
     
     
         2 . The cell according to  claim 1 , which is a T cell. 
     
     
         3 . The cell according to  claim 2 , which is a CD4 positive T cell. 
     
     
         4 . The cell according to  claim 3 , which is a follicular B helper T cell (TFH cell). 
     
     
         5 . The cell according to  claim 3 , wherein increase in expression level of CD25 and secretion of at least one of galectin-9 and interleukin 10 (IL-10) are induced by T cell receptor (TCR) stimulation. 
     
     
         6 . The cell according to  claim 3 , which does not express Foxp3. 
     
     
         7 . The cell according to  claim 2 , which is a γδT cell. 
     
     
         8 . The cell according to  claim 1 , which is a natural killer cell (NK cell). 
     
     
         9 . The cell according to  claim 1 , which is a B cell. 
     
     
         10 . The cell according to  claim 1 , which is a NKT cell. 
     
     
         11 . The cell according to  claim 1 , which is a conventional dendritic cell (cDC). 
     
     
         12 . The cell according to  claim 1 , which is a plasmacytoid dendritic cell (pDC). 
     
     
         13 . The cell according to  claim 1 , which is a pDC-like macrophage (pDC-Mφ. 
     
     
         14 . A method for producing the cell according to  claim 1 , the method comprising:
 administering galectin-9 to an animal, thus inducing galectin-9 expression on a cell surface of at least one cell in the animal.   
     
     
         15 . A method for producing the cell according to  claim 1 , the method comprising:
 culturing one or more cells of an animal in the presence of galectin-9, thus inducing galectin-9 expression on a cell surface of at least one of the cells.   
     
     
         16 . The production method according to  claim 15 , wherein
 the cells of the animal comprise a cell expressing galectin-9 on a cell surface, and   by culturing the cells in the presence of galectin-9, the proportion of the cell expressing galectin-9 on the cell surface is increased.   
     
     
         17 . The production method according to  claim 14 , wherein the animal is a mammal. 
     
     
         18 . The production method according to  claim 17 , wherein the mammal is a human. 
     
     
         19 . A pharmaceutical agent comprising:
 at least one selected from the group consisting of: the cell according to  claim 1 ; homogenates of the cell; and extracts of the cell.   
     
     
         20 . The pharmaceutical agent according to  claim 19 , for use in treatment or reduction of a symptom of a disease caused by deficiency or absence of physiological activity or biological activity of galectin-9. 
     
     
         21 . The pharmaceutical agent according to  claim 19 , which is a diagnostic agent for use in diagnosis of the presence or absence of a cell that contains galectin-9 or a galectin-9-binding substance. 
     
     
         22 . The pharmaceutical agent according to  claim 19 , which is an immunomodulatory agent. 
     
     
         23 . The pharmaceutical agent according to  claim 19 , which is an anti-tumor agent. 
     
     
         24 . The pharmaceutical agent according to  claim 23 , wherein the tumor is a malignant tumor. 
     
     
         25 . The pharmaceutical agent according to  claim 24 , wherein the malignant tumor is an epithelial malignant tumor. 
     
     
         26 . The pharmaceutical agent according to  claim 24 , wherein the malignant tumor is a non-epithelial malignant tumor. 
     
     
         27 . The pharmaceutical agent according to  claim 26 , wherein the non-epithelial malignant tumor is at least one of a tumorigenic non-epithelial malignant tumor and a non-tumorigenic non-epithelial malignant tumor. 
     
     
         28 . The pharmaceutical agent according to  claim 24 , wherein the malignant tumor is at least one selected from the group consisting of skin cancers, melanomas, breast cancers, ovarian cancers, uterine cancers, malignant testicular tumors, prostate cancers, bladder cancers, kidney cancers, thyroid cancers, pharyngeal and laryngeal cancers, tongue cancers, maxillary cancers, esophageal cancers, stomach cancers, colon and rectal cancers, lung and bronchial cancers, liver cancers, hepatocellular cancers, intrahepatic bile duct cancers, extrahepatic bile duct and gallbladder cancers, pancreatic cancers, leukemia, malignant lymphoma, plasmacytoma, sarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, fibrosarcoma, malignant hemangioma, malignant hemangioendothelioma, brain tumors, meningioma, glioma, and astrocytoma. 
     
     
         29 . The pharmaceutical agent according to  claim 19 , which is an anti-allergic agent. 
     
     
         30 . The pharmaceutical agent according to  claim 19 , which is an anti-autoimmune disease agent. 
     
     
         31 . The pharmaceutical agent according to  claim 19 , which is an anti-inflammatory agent. 
     
     
         32 . The pharmaceutical agent according to  claim 19 , which is an alternate agent for adrenocortical steroid hormone. 
     
     
         33 . The pharmaceutical agent according to  claim 19 , which is an inhibitor for transplantation rejection accompanying transplantation of a cell, a tissue, or an organ. 
     
     
         34 . The pharmaceutical agent according to  claim 19 , for use in treatment or reduction of a symptom of sepsis. 
     
     
         35 . The pharmaceutical agent according to  claim 19 , for use in treatment or reduction of a symptom of an infectious disease. 
     
     
         36 . A method for diagnosing the presence or absence of galectin-9 or a galectin-9-binding substance in a test cell using at least one selected from the group consisting of: the cell according to  claim 1 ; homogenates of the cell; and extracts of the cell. 
     
     
         37 . A method for treating a disease of an animal or reducing a symptom caused by the disease, the method comprising the step of:
 administering to the animal at least one selected from the group consisting of: the cell according to  claim 1 ; homogenates of the cell; and extracts of the cell.   
     
     
         38 . The method according to  claim 37 , wherein the animal is a mammal. 
     
     
         39 . The method according to  claim 38 , wherein the mammal is a human. 
     
     
         40 . The method according to  claim 37 , wherein the disease is caused by the deficiency or absence of physiological activity or biological activity of galectin-9. 
     
     
         41 . The method according to  claim 37 , wherein the disease is caused by immune abnormality. 
     
     
         42 . The method according to  claim 37 , wherein the disease is an autoimmune disease. 
     
     
         43 . The method according to  claim 37 , wherein the disease is a tumor. 
     
     
         44 . The method according to  claim 43 , wherein the tumor is a malignant tumor. 
     
     
         45 . The method according to  claim 44 , wherein the malignant tumor is an epithelial malignant tumor. 
     
     
         46 . The method according to  claim 44 , wherein the malignant tumor is a non-epithelial malignant tumor. 
     
     
         47 . The method according to  claim 46 , wherein the non-epithelial malignant tumor is at least one of a tumorigenic non-epithelial malignant tumor and a non-tumorigenic non-epithelial malignant tumor. 
     
     
         48 . The method according to  claim 44 , wherein the malignant tumor is at least one selected from the group consisting of skin cancers, melanomas, breast cancers, ovarian cancers, uterine cancers, malignant testicular tumors, prostate cancers, bladder cancers, kidney cancers, thyroid cancers, pharyngeal and laryngeal cancers, tongue cancers, maxillary cancers, esophageal cancers, stomach cancers, colon and rectal cancers, lung and bronchial cancers, liver cancers, hepatocellular cancers, intrahepatic bile duct cancers, extrahepatic bile duct and gallbladder cancers, pancreatic cancers, leukemia, malignant lymphoma, plasmacytoma, sarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, fibrosarcoma, malignant hemangioma, malignant hemangioendothelioma, brain tumors, meningioma, glioma, and astrocytoma. 
     
     
         49 . The method according to  claim 37 , wherein the disease is an allergic disease. 
     
     
         50 . The method according to  claim 37 , wherein the disease is transplantation rejection accompanying transplantation of a cell, a tissue, or an organ. 
     
     
         51 . The method according to  claim 37 , wherein the disease is sepsis. 
     
     
         52 . The method according to  claim 37 , wherein the disease is an infectious disease. 
     
     
         53 . The method according to  claim 37 , wherein the symptom caused by the disease is inflammation. 
     
     
         54 . A method for regulating immunity of an animal, the method comprising the step of:
 administering the cell according to  claim 1  to the animal.   
     
     
         55 . A method for detecting the cell according to  claim 1 , the method comprising the step of:
 detecting the galectin-9 expressed on the cell surface of the cell as a marker.   
     
     
         56 . The cell detection method according to  claim 55 , wherein the cell according to  claim 1  is an IL-10-producing type 1 regulatory T cell (Tr1 cell). 
     
     
         57 . The cell detection method according to  claim 55 , wherein the cell according to  claim 1  is a regulatory immune cell. 
     
     
         58 . A method for diagnosing a disease of an animal or a symptom caused by the disease, the method comprising the step of:
 in a tissue of the animal containing or not containing the cell according to  claim 1 , detecting the cell according to  claim 1  qualitatively or quantitatively by detecting the galectin-9 expressed on the cell surface of the cell as a marker.   
     
     
         59 . A method for determining a therapeutic effect on a disease of an animal, the method comprising the steps of:
 treating the disease of the animal;   diagnosing the disease or a symptom caused by the disease by the diagnostic method according to  claim 58  before and after the treatment; and   comparing diagnostic results obtained before and after the treatment.   
     
     
         60 . A cell separation method comprising the steps of:
 in a tissue of an animal containing the cell according to  claim 1 , detecting the cell by detecting the galectin-9 expressed on the cell surface of the cell as a marker; and   separating the detected cell from other cells in the tissue of the animal.   
     
     
         61 . A method for producing the cell according to  claim 1 , comprising the step of:
 separating the cell according to  claim 1  from a tissue of an animal by a cell separation method comprising the steps of:   in a tissue of the animal containing the cell according to  claim 1 , detecting the cell by detecting the galectin-9 expressed on the cell surface of the cell as a marker; and   separating the detected cell from other cells in the tissue of the animal.   
     
     
         62 . A method for producing the cell according to  claim 1 , the method comprising:
 administering galectin-9 to an animal, thus inducing galectin-9 expression on a cell surface of at least one cell in the animal, and   separating the cell according to  claim 1  from a tissue of the animal by a cell separation method comprising the steps of:   in a tissue of the animal containing the cell according to  claim 1 , detecting the cell by detecting the galectin-9 expressed on the cell surface of the cell as a marker; and   separating the detected cell from other cells in the tissue of the animal.