NLRX1: A New Therapeutic Target for Inflammatory Bowel Disease
March 15 2017
BLACKSBURG, VA. March, 2017 – The Landos Biopharma, Inc. (LANDOS) team recently characterized a new mechanism of action underlying the regulation of immunity and metabolism by nucleotide oligomerization domain like receptor X1 (NLRX1), an immunoregulatory target implicated in antiviral immune responses. We provide evidence that the new NLRX1 mechanism synchronizes immunity and metabolism.
The findings were published in a recent paper in the Journal of Immunology.
The loss of NLRX1 results in an increase in inflammatory T cells in the gut of mouse models of inflammatory bowel disease (IBD) coinciding with a shift in metabolic function. Specifically, NLRX1 deficiency diverts resources from the citric acid cycle and allocates them toward the production of lactate. Interestingly, when this shift is prevented, NLRX1-deficient T cells behave no differently than a wild type cell.
Due to an incomplete understanding of the conditions surrounding NLRX1, targeting this molecule as a potential therapy had previously stalled. The results in the Journal of Immunology paper by the LANDOS team shed new mechanistic insights on the role of NLRX1 in mucosal immunity and metabolism.
The discovery of NLRX1 on the immunometabolic interface lends support that nutrition and cellular metabolism are intimately linked with immune function. As such, immunoregulatory molecules like NLRX1, PPARs, or lanthionine synthetase C-like 2 (LANCL2) are new therapeutic targets applicable to a spectrum of immune-mediated diseases.
The need to produce energy is inherent to all cells within the body. However, as research delves into the field of immunometabolism, it has become clear that inflammatory, regulatory and memory cells have distinct patterns of metabolic preferences across not only T cells, but also macrophages and dendritic cells as well epithelial cells and their functional subsets. Whether fulfilling a need to proliferate, produce cytokines, or sustain a long lifespan, the targeting of cellular metabolism offers new therapeutic possibilities beyond traditional immunological targets in immune-mediated disease.
“For decades, immunologists have applied reductionist approaches to studying the smallest details of the immune response without considering crucial system-wide interactions with nutrition and metabolism,” said Josep Bassaganya-Riera, LANDOS President and CEO, and the corresponding author of the paper. “Landos has built computational and mathematical models capable of analyzing complex massively interacting systems, including interactions between immunity and metabolism. This study not only elucidates novel mechanisms of immunoregulation in IBD, but it also validates transcriptomic and computational modeling studies that predicted the importance of NLRX1 in regulating gastrointestinal inflammation and its potential as a therapeutic target for infectious and autoimmune diseases.”
LANDOS is at the forefront of developing oral therapies for immune-mediated diseases, most prominently IBD. Additional exploration into immunometabolism may hold the reasons as to why dietary compounds and microbiota components can provide critical immunological feedback that ameliorates disease and pathology.
About LANDOS – Accelerated Path to Cures
Landos Biopharma, Inc. is an emerging biopharmaceutical company focused on the discovery and development of innovative first-in-class, oral therapeutics for patients with autoimmune diseases. Landos’ lead clinical asset, BT-11, is a novel, locally acting small molecule targeting inflammatory bowel disease (IBD) that is expected to enter clinical testing for Crohn’s disease in 2018. Landos also has a robust pipeline of compounds for other autoimmune diseases.
Landos is headquartered in Blacksburg, Virginia. For more information, please visit www.landosbiopharma.com or contact [email protected].
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