Use of inosine for the treatment of t-reg deficiency
The present invention provides the use of inosine in the treatment of a disease associated with Treg deficiency or Treg dysfunction, in particular immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). In one embodiment of the invention, the inosine can be provided in the form of a bacterial strain that is capable of stimulating the production of inosine. Methods for stimulating the production of inosine in a subject using said strains are also provided, as are methods for the selection of a bacterial strain capable of stimulating inosine production in a subject.
1. An in vivo method for selecting a lactic acid bacterial strain capable of stimulating inosine production, wherein the method comprises detecting or determining the amount or level of inosine stimulation by a bacterial strain by:
a) administering a bacterial strain to a suitable animal model;
b) obtaining samples from the animal model;
c) measuring the levels of inosine in the sample;
and selecting a bacterial strain which has the ability to stimulate inosine production in vivo.
2. The method of claim 1 , wherein the animal model is an experimental mouse model system.
3. The method of claim 1 , wherein the selected strain is Lactobacillus reuteri.
4. The method of claim 1 , further comprising culturing or propagating or producing the bacterial strain.
5. The method of claim 1 , wherein the sample is a systemic sample or a stool or GI tract sample.
6. The method of claim 5 , wherein the systemic sample is a plasma, blood, or serum sample.
7. The method of claim 1 , wherein the method comprises measuring the levels of inosine without administration of the bacterial strain and comparing the levels of inosine in step (c) to the levels observed in the absence of the strain.
8. The method of claim 1 , wherein the selected strain is not Lactobacillus reuteri DSM 17938.
9. The method of claim 1 , wherein the experimental mouse model system is a scurfy mouse model.
10. The method of claim 7 , wherein the experimental mouse model system is a scurfy mouse model.
11. The method of claim 7 , wherein the selected strain is not Lactobacillus reuteri DSM 17938.
12. The method of claim 1 , further comprising lyophilizing or freeze drying the bacterial strain.