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J Cell Physiol. 2020 Mar;235(3):1895-1902. doi: 10.1002/jcp.29161. Epub 2019 Sep 4.

CARD14/CARMA2sh and TANK differentially regulate poly(I:C)-induced inflammatory reaction in keratinocytes.

Author information

1
Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, Italy.
2
Genus Biotech, Università del Sannio, Benevento, Italy.
3
Consorzio Sannio Tech, Strada Statale Appia, Benevento, Benevento, Italy.

Abstract

CARD14/CARMA2sh (CARMA2sh) is a scaffold protein whose mutations are associated with the onset of human genetic psoriasis and other inflammatory skin disorders. Here we show that the immunomodulatory adapter protein TRAF family member-associated NF-κB activator (TANK) forms a complex with CARMA2sh and MALT1 in a human keratinocytic cell line. We also show that CARMA2 and TANK are individually required to activate the nuclear factor κB (NF-κB) response following exposure to polyinosinic-polycytidylic (poly [I:C]), an agonist of toll-like receptor 3. Finally, we present data indicating that TANK is essential for activation of the TBK1/IRF3 pathway following poly (I:C) stimulation, whereas CARMA2sh functions as a repressor of it. More important, we report that two CARMA2sh mutants associated with psoriasis bind less efficiently to TANK and are therefore less effective in suppressing the TBK1/IRF3 pathway. Overall, our data indicate that TANK and CARMA2sh regulate TLR3 signaling in human keratinocytes, which could play a role in the pathophysiology of psoriasis.

KEYWORDS:

CARD14/CARMA2; Poly (I:C); TANK; TBK1; psoriasis

PMID:
31486084
DOI:
10.1002/jcp.29161

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