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The NLR family pyrin domain containing 11 protein contributes to the regulation of inflammatory signalling.

The NLR family pyrin domain containing 11 protein contributes to the regulation of inflammatory signalling.
Author Information (click to view)

Ellwanger K, Becker E, Kienes I, Sowa A, Postma Y, Gloria YC, Weber ANR, Kufer TA,


Ellwanger K, Becker E, Kienes I, Sowa A, Postma Y, Gloria YC, Weber ANR, Kufer TA, (click to view)

Ellwanger K, Becker E, Kienes I, Sowa A, Postma Y, Gloria YC, Weber ANR, Kufer TA,

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The Journal of biological chemistry 2018 01 04() pii jbc.RA117.000152
Abstract

Mammalian NLR proteins contribute to the regulation and induction of innate and adaptive immunity in mammals although the function of about half of the currently identified NLR proteins remains poorly characterized. Here we analysed the function of the primate-specific NLRP11 gene product. We show that NLRP11 is highly expressed in immune cells, including myeloid cells, B cells and some B cell lymphoma lines. Overexpression of NLRP11 in human cells did not trigger key innate immune signalling pathways including NF-κB and type I interferon responses. NLRP11 harbours a pyrin domain (PYD), which is responsible for inflammasome formation in related NLR proteins. However, NLRP11 did neither interact with the inflammasome adaptor protein ASC nor did it trigger caspase-1 activation. By contrast, expression of NLRP11 specifically repressed NF-κB and type I interferon responses, two key innate immune pathways involved in inflammation. This effect was independent of the PYD domain and ATPase activity of NLRP11. SiRNA-mediated knock-down of NLRP11 in human myeloid THP1 cells validated these findings and revealed enhanced lipopolysaccharide (LPS) and Sendai Virus (SeV)-induced cytokine and interferon responses, respectively in cells with reduced NLRP11 expression. In summary, our work identifies a novel role of NLRP11 in the regulation of inflammatory responses in human cells.

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