Available online 5 May 2022, 108198

Abnormal regulation of pro-inflammatory cytokine and chemokine mediators can contribute to the excess inflammation characteristic of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, Crohn's disease, type 1 diabetes, and many others. The tristetraprolin (TTP) family consists of a small group of related RNA-binding proteins that bind to preferred AU-rich binding sites within the 3′-untranslated regions of specific mRNAs to promote mRNA deadenylation and decay. TTP deficient mice develop a severe systemic inflammatory syndrome consisting of arthritis, myeloid hyperplasia, dermatitis, autoimmunity and cachexia, due at least in part to the to the excess accumulation of proinflammatory chemokine and cytokine mRNAs and their encoded proteins. To investigate the possibility that increased TTP expression or activity might have a beneficial effect on inflammatory diseases, at least two mouse models have been developed that provide proof of principle that increasing TTP activity can promote the decay of pro-inflammatory and other relevant transcripts, and decrease the severity of mouse models of inflammatory disease. Animal studies of this type are summarized here, and we briefly review the prospects for harnessing these insights for the development of TTP-based anti-inflammatory treatments in humans.

RNA-binding protein

Tristetraprolin (TTP)

Zfp36

Cytokines

Inflammation

Tumor necrosis factor

bone marrow-derived macrophages

3′-untranslated regions

mitogen activated protein

NOT1 binding domain

granulocyte macrophage colony-stimulating factor

collagen antibody-induced arthritis

hematoxylin and eosin

experimental autoimmune encephalitis

myelin oligodendrocyte glycoprotein

tartrate-resistant acid phosphate

experimental autoimmune uveitis

interphotoreceptor retinoid-binding protein

bronchoalveolar lavage fluid

hematopoietic progenitor cells

7,12-dimethylbenz[a]anthracene

12–0 tetradecanoylphorbol-13-acetate

spasmolytic polypeptide-expressing metaplasia

MAPK-activated protein kinase 2

chronic obstructive pulmonary disease

© 2022 Published by Elsevier Inc.