Editorial
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 28, 2013; 19(28): 4447-4454
Published online Jul 28, 2013. doi: 10.3748/wjg.v19.i28.4447
Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature
Györgyi Műzes, Zsolt Tulassay, Ferenc Sipos
Györgyi Műzes, Zsolt Tulassay, Ferenc Sipos, 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary
Author contributions: Műzes G wrote the manuscript; Tulassay Z and Sipos F contributed in editing and revising the manuscript.
Correspondence to: Györgyi Műzes, MD, PhD, Associate Professor of Immunology and Internal Medicine, 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str. 46, 1088 Budapest, Hungary. muzes.gyorgyi@med.semmelweis-univ.hu
Telephone: +36-12-660926 Fax: +36-12-660816
Received: May 29, 2013
Revised: June 19, 2013
Accepted: July 4, 2013
Published online: July 28, 2013
Processing time: 61 Days and 9.9 Hours
Abstract

Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. Recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IRGM, NOD2, XBP1) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.

Keywords: Crohn's disease; Innate immunity; Autophagy genes; Autophagy; Gut microbiota

Core tip: In case of Crohn's disease, on the basis of autophagy-related risk genetic polymorphisms impaired sensing and responding of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy represents a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis.