Nucleotide-Binding Domain Leucine-Rich Repeat Containing Proteins and Intestinal Microbiota: Pivotal Players in Colitis and Colitis-Associated Cancer Development.

Anna Prossomariti,Luigi Ricciardiello,Harry Sokol

doi:10.3389/fimmu.2018.01039

Abstract

The nucleotide-binding domain leucine-rich repeat containing (NLR) proteins play a fundamental role in innate immunity and intestinal tissue repair. A dysbiotic intestinal microbiota, developed as a consequence of alterations in NLR proteins, has recently emerged as a crucial hit for the development of ulcerative colitis (UC) and colitis-associated cancer (CAC). The concept of the existence of functional axes interconnecting bacteria with NLR proteins in a causal role in intestinal inflammation and CAC aroused a great interest for the potential development of preventive and therapeutic strategies against UC and CAC. However, the most recent scientific evidence, which highlights many confounding factors in studies based on microbiota characterization, underlines the need for an in-depth reconsideration of the data obtained until now. The purpose of this review is to discuss the recent findings concerning the cross talk between the NLR signaling and the intestinal microbiota in UC and CAC development, and to highlight the open issues that should be explored and addressed in future studies.

Highlights

Under physiological conditions, a delicate balance between immune activation and self-tolerance, resulting from a beneficial mutualistic relationship with the host gut microbial community, is responsible for maintaining a healthy intestinal homeostasis
pattern recognition receptors (PRRs) families can be classified as transmembrane receptors, including toll-like receptors and C-type lectins receptors, responsible for recognizing extracellular and endosomal-derived pathogen-associated molecular patterns (PAMPs); and cytosolic receptors including retinoic acid-inducible gene-I-like receptors and nucleotide-binding domain leucine-rich repeat containing (NLRs) proteins, involved in the intracellular surveillance toward infections and recognition of self-derived damage-associated molecular patterns (DAMPs) [4]
Functional studies aiming at clarifying the role of NLR proteins in the development of colitis and CAC have been mainly performed on pre-clinical models, observational and association studies conducted in humans partially support a protective role of some NLR proteins on inflammatory bowel disease (IBD) onset and progression

Summary

Frontiers in Immunology

The nucleotide-binding domain leucine-rich repeat containing (NLR) proteins play a fundamental role in innate immunity and intestinal tissue repair. A dysbiotic intestinal microbiota, developed as a consequence of alterations in NLR proteins, has recently emerged as a crucial hit for the development of ulcerative colitis (UC) and colitisassociated cancer (CAC). The concept of the existence of functional axes interconnecting bacteria with NLR proteins in a causal role in intestinal inflammation and CAC aroused a great interest for the potential development of preventive and therapeutic strategies against UC and CAC. The purpose of this review is to discuss the recent findings concerning the cross talk between the NLR signaling and the intestinal microbiota in UC and CAC development, and to highlight the open issues that should be explored and addressed in future studies

INTRODUCTION

ROLE OF NLR PROTEINS IN HUMAN IBD

CONCLUSION