Methods and compositions for inhibition of innate immune responses and autoimmunity

1. A method of inhibiting a TLR7/8 dependent immune response in an individual, wherein the individual is a human, the method comprising administering to the individual a composition comprising an oligonucleotide, in an amount sufficient to inhibit the TLR7/8 dependent immune response in said individual, wherein the oligonucleotide comprises SEQ ID NO: 105 or an analog of SEQ ID NO: 105 at the 5′ end of the oligonucleotide, the oligonucleotide is less than 50 bases or base pairs and does not comprise a CG dinucleotide, and wherein in the analog of SEQ ID NO: 105 one or two principal bases other than TGC of SEQ ID NO: 105 are each replaced with a naturally or occurring base or a modified, non-naturally occurring base.

2. A method of regulating a TLR7/8 dependent and/or TLR9 dependent immune response in an individual, comprising administering to the individual an oligonucleotide comprising the nucleotide sequence: 5′-TGCN m TCCTGGAGGGGTTGT-3′ (SEQ ID NO:6), wherein each N is a nucleotide and m is an integer from 0 to 100, in an amount sufficient to regulate the immune response in said individual.

3. A method of suppressing TLR7/8 dependent cytokine production in an individual, wherein the individual is a human, the method comprising administering to the individual a composition comprising an oligonucleotide, in an amount sufficient to suppress TLR7/8 dependent cytokine production in said individual, wherein the oligonucleotide comprises SEQ ID NO: 105 or an analog of SEQ ID NO: 105 at the 5′ end of the oligonucleotide, the oligonucleotide is less than 50 bases or base pairs and does not comprise a CG dinucleotide, and wherein in the analog of SEQ ID NO: 105 one or two principal bases other than TGC of SEQ ID NO: 105 are each replaced with a naturally or non naturally occurring base or a modified, non-naturally occurring base.

4. A method of suppressing TLR9 dependent cytokine production and TLR7/8 dependent cytokine production in an individual, wherein the individual is a human, the method comprising administering to the individual a composition comprising an oligonucleotide, in an amount sufficient to suppress TLR9 dependent cytokine production and TLR7/8 dependent cytokine production in said individual, wherein the oligonucleotide comprises SEQ ID NO: 103 or an analog of SEQ ID NO: 103 at the 5′ end of the oligonucleotide, the oligonucleotide is less than 50 bases or base pairs and does not comprise a CG dinucleotide, and wherein in the analog of SEQ ID NO: 103 one or two principal bases other than TGC of SEQ ID NO: 103 are each replaced with a naturally occurring base or a modified, non-naturally occurring base.

5. The method of claim 1 , wherein the oligonucleotide comprises a 5′-GGGG-3′ sequence.

6. The method of claim 1 , wherein the oligonucleotide is selected from the group consisting of SEQ ID NO:52 and SEQ ID NO:114.

7. The method of claim 3 , wherein the oligonucleotide comprises a 5′-GGGG-3′ sequence.

8. The method of claim 3 , wherein the oligonucleotide is selected from the group consisting of SEQ ID NO:52 and SEQ ID NO:114.

9. The method of claim 4 , wherein the oligonucleotide comprises a 5′-GGGG-3′ sequence.

10. The method of claim 4 , wherein the oligonucleotide is selected from the group consisting of SEQ ID NO:52 and SEQ ID NO: 114.

11. The method of claim 1 , wherein the oligonucleotide contains phosphate-modified linkages.

12. The method of claim 11 , wherein the oligonucleotide contains only phosphorothioate linkages.

13. The method of claim 2 , wherein the oligonucleotide contains phosphate-modified linkages.

14. The method of claim 13 , wherein the oligonucleotide contains only phosphorothioate linkages.

15. The method of claim 3 , wherein the oligonucleotide contains phosphate-modified linkages.

16. The method of claim 15 , wherein the oligonucleotide contains only phosphorothioate linkages.

17. The method of claim 4 , wherein the oligonucleotide contains phosphate-modified linkages.

18. The method of claim 17 , wherein the oligonucleotide contains only phosphorothioate linkages.

19. The method of claim 1 , wherein the oligonucleotide comprises one of the group consisting of SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104 and SEQ ID NO:105.

20. The method of claim 1 , wherein the oligonucleotide comprises an analog of SEQ ID NO: 105 in which one of said principal bases other than the TGC is replaced with said naturally occurring base or said modified, non-naturally occurring base.

21. The method of claim 1 , wherein the oligonucleotide is less than 40 bases in length.

22. The method of claim 21 , wherein the oligonucleotide is less than 20 bases in length.

23. The method of claim 2 , wherein the oligonucleotide is less than 40 bases in length.

24. The method of claim 23 , wherein the oligonucleotide is less than 20 bases in length.

25. The method of claim 3 , wherein the oligonucleotide comprises one of the group consisting of SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104 and SEQ ID NO:105.

26. The method of claim 3 , wherein the oligonucleotide comprises an analog of SEQ ID NO: 105 in which one of said principal bases other than the TGC is replaced with said naturally occurring base or said modified, non-naturally occurring base.

27. The method of claim 3 , wherein the oligonucleotide is less than 40 bases in length.

28. The method of claim 27 , wherein the oligonucleotide is less than 20 bases in length.

29. The method of claim 4 , wherein the oligonucleotide comprises one of the group consisting of SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, and SEQ ID NO:103.

30. The method of claim 4 , wherein the oligonucleotide comprises an analog of SEQ ID NO: 103 in which one of said principal bases other than the TGC is replaced with said naturally occurring base or said modified, non-naturally occurring base.

31. The method of claim 4 , wherein the oligonucleotide is less than 40 bases in length.

32. The method of claim 31 , wherein the oligonucleotide is less than 20 bases in length.