NLRP6 Deficiency in CD4 T Cells Decreases T Cell Survival Associated with Increased Cell Death

Abstract

The nucleotide-binding oligomerization domain (NOD)-like receptors belong to the family of pattern recognition receptors (PRRs). NOD-like receptors play a role in regulation of innate immune response by recognition of both pathogen-associated molecular patterns that are engulfed during phagocytic process and danger-associated molecular patterns that are mainly byproducts of cell stress mediated response. NOD-like family pyrin domain containing 6 (NLRP6) is one of the 14 pyrin domain-containing receptors. NLRP6 is highly expressed by epithelial and goblet cells to regulate epithelial renewal and mucus production in mice and humans, but its function in T cells is rather unknown. Increased caspase-1 activation and cell death were observed in mouse Nlrp6-deficient T cells following adoptive transfer into Rag2-deficient mice, indicating that Nlrp6 deficiency in CD4 + T cells led to decreased survival.

Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis

“…Cell Isolation from the small and large intestinal lamina propria, mesenteric lymph nodes and spleen Colonic lamina propria cells were isolated as described previously (Radulovic et al, 2019;Steinert et al, 2017). Briefly, extracted colon or small intestine segments were opened longitudinally and washed with PBS (Sigma-Aldrich).…”

Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles

“…NLRP6 is highly expressed in the digestive system 20 , 24 and most of the functional studies of NLRP6 focus on this system and its related diseases. However, NLRP6 is also expressed in other tissues such as the kidney, liver and lung and in cells such as neurons, lymphocytes, or bone marrow-derived cells 7 , 20 , 25 . NLRP6 is a gene with multiple alternative transcriptional promoters that determine its distribution and expression across selective tissue and cell types 24 .…”

“…In addition to epithelial cells, NLRP6 is also expressed in different cells of the innate and adaptive immune system, including T cells, monocytes, and neutrophils 7 , 22 , 25 , 51 . In Th1 cells, NLRP6 expression is controlled by the transcription factor TBX21, where it facilitates T cell survival 25 (Fig. 2a ).…”

Tissue-selective alternate promoters guide NLRP6 expression

“…In the intestine, Nlrp6 RNA expression has been found primarily in enterocytes and colonic goblet cells (Chen et al, 2011;Elinav et al, 2011;Normand et al, 2011). It has also been described in various circulating immune cell populations including macrophages and lymphocytes measured by relative RNA expression (Hara et al, 2018;Radulovic et al, 2019). To establish which cells within the kidney express Nlrp6Δ59UTR, we fractionated fresh single-cell kidney preparations across a density gradient and sorted the samples by flow cytometry before absolute quantification by real-time PCR.…”

“…NLRP6 protein is most highly expressed in the intestinal epithelium where it has been associated with regulating mucosal host-microbiota interactions (Normand et al, 2011;Gremel et al, 2014;Wang et al, 2015). Despite restriction at the protein level, a number of reports in mice have documented Nlrp6 RNA within broad tissue types including the kidney, liver, lung, lymphocytes, and bone marrow-derived cells (Elinav et al, 2011;Hara et al, 2018;Radulovic et al, 2019). Many PYD-containing genes show similarly diverse expression profiles.…”