A method comprising administering, to a subject in need thereof, an effective amount of a nucleotide effective to disrupt one or more pathways leading to sepsis. The nucleotide may be a nitric oxide disruptor effective to decrease the expression of inducible nitric oxide synthase. The nitric oxide disrupter may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 1 through Sequence ID No. 47. Additionally or alternatively, the nucleotide may be an α disintegrin and metalloproteinase (ADAM) enzyme inhibitor effective to decrease the expression of ADAM enzyme. The ADAM enzyme inhibitor may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 48 through Sequence ID No. 56.

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R.sup.58, R.sup.56 and K.sup.57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

A method comprising administering, to a subject in need thereof, an effective amount of a nucleotide effective to disrupt one or more pathways leading to sepsis. The nucleotide may be a nitric oxide disruptor effective to decrease the expression of inducible nitric oxide synthase. The nitric oxide disrupter may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 1 through Sequence ID No. 47. Additionally or alternatively, the nucleotide may be an α disintegrin and metalloproteinase (ADAM) enzyme inhibitor effective to decrease the expression of ADAM enzyme. The ADAM enzyme inhibitor may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 48 through Sequence ID No. 56.

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R.sup.58, R.sup.56 and K.sup.57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R.sup.58, R.sup.56 and K.sup.57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

Engineered immune cells, optionally natural killer (NK) cells, comprising an inactivating mutation for an endogenous A-Disintegrin-And-Metalloproteinase 17 (ADAM 17) gene. ADAM17-deficient immune cells produced from stem cells, optionally, induced pluripotent stem cells (iPSCs), having enhanced antibody-dependent cellular cytotoxicity (ADCC). Pharmaceutical compositions comprising said engineered immune cells. Methods for making the engineered immune cell and pharmaceutical compositions, and methods of use are provided.

A method comprising administering, to a subject in need thereof, an effective amount of a nucleotide effective to disrupt one or more pathways leading to sepsis. The nucleotide may be a nitric oxide disruptor effective to decrease the expression of inducible nitric oxide synthase. The nitric oxide disrupter may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No.1 through Sequence ID No. 47. Additionally or alternatively, the nucleotide may be an disintegrin and metalloproteinase (ADAM) enzyme inhibitor effective to decrease the expression of ADAM enzyme. The ADAM enzyme inhibitor may comprise a polynucleotide strand exhibiting at least 70% sequence identity to one of Sequence ID No. 48 through Sequence ID No. 56.

Disclosed is a gene/carrier complex for preventing or treating inflammatory diseases, including tumor necrosis factor- converting enzyme (TNF- converting enzyme, TACE) shRNA and a nonviral gene carrier, wherein the nonviral gene carrier includes an acetate of disulfide-linked poly(oligo-arginine) or a TFA salt of poly(oligo-aspartic acid)poly(oligo-arginine).

Provided herein are methods and compositions related to TREM2 mutants resistant to sheddase cleavage, e.g., human TREM2 mutants resistant to sheddase cleavage, and nucleic acids encoding such TREM2 mutants resistant to sheddase cleavage.

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R.sup.58, R.sup.56 and K.sup.57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.