Research ArticleImmunology

The kinase TPL2 activates ERK and p38 signaling to promote neutrophilic inflammation

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Sci. Signal.  18 Apr 2017:
Vol. 10, Issue 475, eaah4273
DOI: 10.1126/scisignal.aah4273

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Targeting inflammatory neutrophils

Neutrophils and monocytes are innate immune cells that establish an inflammatory response to infection. Because of their numbers, neutrophils produce substantial amounts of inflammatory cytokines; thus, targeting them specifically would help in the treatment of chronic inflammatory diseases. Senger et al. found that the kinase TPL2, which activates the ERK family of mitogen-activated protein kinases (MAPKs) in immune cells, also stimulated p38 MAPK activity specifically in neutrophils. TPL2 activity was greater in tissues from patients with Crohn’s disease or rheumatoid arthritis than in those from healthy donors. Mice with a kinase-deficient form of TPL2 or that were treated with a small-molecule inhibitor of TPL2 had decreased neutrophil-dependent inflammation, which suggests that targeting TPL2 may provide a therapy to treat patients with inflammatory diseases.