Indole regulation of antigen presenting cells
The disclosure provides methods and compositions for affecting the development of antigen presenting cell (APC, e.g., a macrophage or dendritic cell). The methods include maturing an APC, promoting anti-inflammatory phenotype, promoting development of a T regulatory cell (Treg) from a naive T cell. The methods generally include exposing an APC to a tryptophan derived microbiota metabolite (TDMM), such as an anti-inflammatory or pro-mucosal TDMM, and permitting the APC to mature. In some embodiments, the conditioned APC is exposed to a naive T cell to further promote development of a T regulatory cell (Treg). In some embodiments, the TDMM is selected from the group consisting of indole, indole-3-acetate, 5-hydroxyindole, and indole-3-pyruvate.
1. A method of maturing an antigen presenting cell (APC), comprising contacting an immature APC in vitro with an effective amount of a composition comprising isolated or purified indole, and permitting maturation of the APC.
2. The method of claim 1 , wherein the APC is a dendritic cell.
3. The method of claim 2 , wherein the APC is a gut-associated lymphoid tissue (GALT) dendritic cell.
4. The method of claim 1 , wherein the APC is a macrophage.
5. The method of claim 1 , further comprising exposing the immature APC to an antigen to which tolerance is desired.
6. The method of claim 1 , wherein the mature APC exhibits an anti-inflammatory phenotype.
7. The method of claim 1 , further comprising exposing the mature APC to a naïve T cell in vivo or ex vivo.
8. A method of promoting anti-inflammatory phenotype, comprising contacting an immature antigen presenting cell (APC) in vitro with a composition comprising isolated or purified indole.
9. The method of claim 8 , wherein promoting anti-inflammatory phenotype comprises promoting peripheral tolerance of antigens in the gut of a subject.
10. The method of claim 8 , wherein the APC is a dendritic cell.
11. The method of claim 10 , wherein the APC is a mucosal dendritic cell.
12. The method of claim 10 , wherein the APC is a gut-associated lymphoid tissue (GALT) dendritic cell.
13. The method of claim 8 , wherein the APC is a macrophage.
14. The method of claim 8 , further comprising administering the exposed APC to the subject.
15. The method of claim 8 , further comprising exposing the mature APC to a naïve T cell in vivo.
16. A method of promoting development of a T regulatory cell (Treg) from a naive T cell, comprising contacting the naive T cell to an antigen presenting cell (APC) that has been conditioned in vitro or ex vivo with a composition comprising isolated or purified indole.
17. The method of claim 16 , wherein the Treg has an increased FoxP3 expression as compared to the naïve T cell.
18. The method of claim 16 , wherein the indole-conditioned APC is produced by contacting an immature APC to the composition comprising the isolated or purified indole and permitted to mature.
19. The method of claim 18 , wherein the APC is a dendritic cell or macrophage.
20. The method of claim 19 , wherein the dendritic cell is a gut-associated lymphoid tissue (GALT) dendritic cell.
21. The method of claim 16 , wherein the Treg is produced in vitro and is administered to a subject in need.