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Although best known for inducing inflammasome formation and pyroptosis in myeloid cells, increasing evidence highlights additional roles for Nod-like receptors (NLR) in nonhematopoietic cells. Two recent studies demonstrate that NLRX1 functions as an intrinsic tumor suppressor in intestinal epithelial cells (IEC), by regulating their responses to proliferative signals following intestinal injury., (Copyright © 2016. Published by Elsevier Ltd.)

While the functional importance of inflammasomes in blood-derived cell types is well established, it remains poorly understood how inflammasomes in nonhematopoietic cells contribute to mucosal immunity. Recent studies have revealed functional roles of inflammasomes - particularly NAIP/NLRC4, NLRP6, and noncanonical caspase-4 (caspase-11) - within epithelial cells of the gut in mucosal immune defense, inflammation, and tumorigenesis. Here, we review and discuss these findings in the broader context of tissue compartment-specific mucosal immunity. We propose several models whereby activities of the intestinal epithelial inflammasomes converge on mechanisms to remove compromised epithelial cells, maintain host-microbiota mutualism, and communicate with immune cells of the underlying lamina propria., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The immune system must constantly monitor the gastrointestinal tract for the presence of pathogens while tolerating trillions of commensal microbiota. It is clear that intestinal microbiota actively modulate the immune system to maintain a mutually beneficial relation, but the mechanisms that maintain homeostasis are not fully understood. Recent advances have begun to shed light on the cellular and molecular factors involved, revealing that a range of microbiota derivatives can influence host immune functions by targeting various cell types, including intestinal epithelial cells, mononuclear phagocytes, innate lymphoid cells, and B and T lymphocytes. Here, we review these findings, highlighting open questions and important challenges to overcome in translating this knowledge into new therapies for intestinal and systemic immune disorders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)