A TLR antagonist comprising an immune regulatory oligonucleotide compound which is an antagonist for one or more TLRs having the structure 5'-N m -N 3 N 2 N 1 CGN 1 N 2 N 3 -N m -3': wherein: CG is an oligonucleotide motif that is CpG, C*pG, C*pG* or CpG*, wherein C is cytosine, C* is a pyrimidine nucleotide derivative which is a pyrimidine nucleotide having a base that is not cytosine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, G is guanosine, and G* is a purine nucleotide derivative which is a purine nucleotide having a base that is not guanine or adenine and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide; N 1 -N 3, at each occurrence, is independently i) a nucleotide, ii) a nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, or iii) a non-nucleotide linkage, provided that at least one N 1 -N 3 is a nucleotide derivative or non-nucleotide linkage that suppresses the activity of the oligonucleotide motif; N 1 -N 3, at each occurrence, is independently i) a nucleotide, or ii) a nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an ol igonucleotide;. N m and N m, at each occurrence, is independently a nucleotide nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, or non-nucleotide linkage; and further provided that the compound contains less than 3 consecutive guanosine nucleotides; wherein the oligonucleotide motif would be immune stimulatory but for the nucleotide derivative or non-nucleotide linkage that suppresses the activity of the oligonucleotide motif; wherein m is a number from 0 to about 30; wherein the immune regulatory oligonucleotide compound is not an antisense oligonucleotide; for use in therapeutically treating or preventing a disease mediated by a TLR in a mammal, wherein the disease is cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen. CG is an oligonucleotide motif that is CpG, C*pG, C*pG* or CpG*, wherein C is cytosine, C* is a pyrimidine nucleotide derivative which is a pyrimidine nucleotide having a base that is not cytosine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, G is guanosine, and G* is a purine nucleotide derivative which is a purine nucleotide having a base that is not guanine or adenine and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide; N 1 -N 3, at each occurrence, is independently i) a nucleotide, ii) a nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, or iii) a non-nucleotide linkage, provided that at least one N 1 -N 3 is a nucleotide derivative or non-nucleotide linkage that suppresses the activity of the oligonucleotide motif; N 1 -N 3, at each occurrence, is independently i) a nucleotide, or ii) a nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an ol igonucleotide;. N m and N m, at each occurrence, is independently a nucleotide nucleotide derivative which is a purine or pyrimidine nucleotide having a base that is not guanine, cytosine, adenine, thymine or uracil and/or a sugar that is not ribose or 2'-deoxyribose and can be present in the backbone of an oligonucleotide, or non-nucleotide linkage; and further provided that the compound contains less than 3 consecutive guanosine nucleotides; wherein the oligonucleotide motif would be immune stimulatory but for the nucleotide derivative or non-nucleotide linkage that suppresses the activity of the oligonucleotide motif; wherein m is a number from 0 to about 30; wherein the immune regulatory oligonucleotide compound is not an antisense oligonucleotide; for use in therapeutically treating or preventing a disease mediated by a TLR in a mammal, wherein the disease is cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.