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Human-derived bacteria that induce proliferation or accumulation of regulatory t cells

A regulatory, bacterial technology applied in the field of human-derived bacteria that induce the proliferation or accumulation of regulatory T cells

Inactive Publication Date: 2014-11-19
THE UNIV OF TOKYO +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although a specific murine commensal bacterial species (NPL 15) that strongly stimulates Tregs has been identified, it is unknown whether human commensal bacterial species exert equivalent effects on the human immune system

Method used

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  • Human-derived bacteria that induce proliferation or accumulation of regulatory t cells
  • Human-derived bacteria that induce proliferation or accumulation of regulatory t cells
  • Human-derived bacteria that induce proliferation or accumulation of regulatory t cells

Examples

Experimental program
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Effect test

Embodiment approach

[0159] The bacterial composition can also be administered to individuals also receiving antibiotic treatment. The present inventors have demonstrated that antibiotics against Gram-positive bacteria such as vancomycin and metronidazole can effectively eliminate or greatly reduce bacterial species belonging to the class Clostridia from the gastrointestinal tract of mammals and subsequently reduce the regulatory T Cellular level (Example 5, Figure 30). Without wishing to be bound by theory, the critical role of bacteria belonging to the Clostridia class in the preservation of immune tolerance strongly suggests that their absence or reduced levels may play a critical role in autoimmune diseases characterized by insufficient immune tolerance . Thus, individuals undergoing a course of antibiotics against Gram-positive bacteria (for example, individuals who are being infected by therapeutic pathogens such as Clostridium difficile and Giardia) who have undergone a deletion of bacteri...

Embodiment 1

[0236] Example 1: First, it was investigated whether the accumulation of regulatory T cells (Treg cells) in the lamina propria of the colon was dependent on commensal bacteria. Specifically, lymphocytes were isolated from the peripheral lymph nodes (pLN) of Balb / c mice fed in the absence of specific pathogenic bacteria (SPF) or from the colon or small intestine (SI) lamina propria of the mice. CD4 and Foxp3 were stained by antibodies. Then, CD4 was analyzed by flow cytometry + Foxp3 in lymphocytes + cell ratio. The results showed that Foxp3 + Treg cells are present at high frequency in the lamina propria of the gastrointestinal tract of mice maintained in a specific pathogen free (SPF) environment, especially the lamina propria of the colon. In addition, it was also found that Foxp3 in the colon lamina propria + The number of Treg cells gradually increased until three months after birth, while Foxp3 in peripheral lymph nodes + The number of Treg cells remains essentially...

Embodiment 2

[0238] Example 2: Next, it was investigated whether the temporal accumulation of Treg cells in the colon found in Example 1 is related to the colonization of the intestinal commensal microbiota. Specifically, the small intestine, colon, and peripheral lymph nodes isolated from mice (8 weeks old: Balb / c mice, IQI mice, and C57BL / 6 mice) fed in a germ-free (GF) or SPF environment were analyzed. CD4 expression and Foxp3 expression in lymphocytes. Similar results were obtained in three or more independent experiments.

[0239] In addition, lamina propria lymphocytes were collected from SPF mice and GF mice (Balb / c mice or C57BL / 6 mice). CD4 and Foxp3 were stained with antibodies. Then, lamina propria lymphocytes were analyzed by FACS.

[0240] In addition, lymphocytes were isolated from colonic lamina propria, small intestinal lamina propria (SI), Peyer's patches (PP) and mesenteric lymph nodes (MLN) of mice administered antibiotics orally with water for eight weeks (SPF C57BL / ...

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Abstract

Species of human-derived bacteria belonging to the Clostridia class have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions. Pharmaceutical compositions containing these bacteria can be used to prevent and treat immune-mediated diseases such as autoimmune diseases.

Description

technical field [0001] The subject matter described herein relates to a composition of human-derived bacteria that induces the proliferation, accumulation, or proliferation and accumulation of regulatory T cells, and said composition comprises as an active ingredient (a) one or more (one , at least one) human-derived bacteria belonging to the Clostridia (Clostridia) class; (b) the culture supernatant of one or more (one, at least one) of the bacteria; (c) from the One or more physiologically active substances obtained from bacteria; or (d) a combination of any two or more of the foregoing. The subject matter described herein also relates to a method for inducing the proliferation, accumulation, or both of regulatory T cells. A composition comprising any of (a)-(d) above is referred to as a bacterial composition. Furthermore, the present subject relates to a method for treating or preventing at least one disease or condition, such as an autoimmune disease, an inflammatory dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N1/20A61K35/74A61P29/00A61P37/02C12N15/09
CPCA61K35/742C12R1/145C12Q2600/156C12N1/20A61K45/06C12Q1/04A61K35/74C12Q1/689A61K35/741A61P29/00A61P31/00A61P33/00A61P37/02A61P37/06A61P37/08C12R2001/145C12N1/205Y02A50/30A61K2035/11A61K9/0053A61K35/745A61K35/747
Inventor 本田贤也新幸二田上大服部正平森田英利
Owner THE UNIV OF TOKYO
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