Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract
Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract
Science, 2005; 307: 731-734
Speaker：張美蘭 Room：601
Commentator：許博翔 醫師 Date：2005/03/30 13:10-14:00
Abstract：
NOD2 (nucleotide-binding oligomerization domain) is a member of NOD1/Apaf-1 family which has conserved N-terminal caspase recruitment domain (CARD) and nucleotide binding domain (NBD). NOD2 was expressed primarily in monocytes, macrophages and dendritic cells1. Muramyl dipeptide (MDP) is a basal component of bacterial peptidoglycan (PGN). MDP can be recognized by NOD2 C-terminal leucine-rich-repeats (LRR), resulting in downstream NFκB activation2. In order to assess the function of NOD2, the authors generated NOD2-/- mice. Frameshift mutant NOD2 functions as a susceptible gene for Crohn’s disease (CD). CD-associated mutant NOD2 can’t activate NFκB in response to MDP stimulation. However, macrophages can activate NFκB signaling in response to bacteria independently of NOD2 to overproduce proinflammatory cytokines, including IL6, IL12, TNF-α and IL-1β resulting in chronic inflammatory disease, CD3. Besides, NOD2-/- mice displayed a severe deficiency in the production of adaptive immunity. By the way, the expression of cryptdins that were regulated by NOD2 in the Paneth cells, was important for host innate immunity. Cryptdins are anti-bacterial peptides that express diminishingly in CD cases. In conclusion, NOD2 is critical to protect the host from intestinal bacterial infection. In a word, what kind of mechanism involved in NOD2 mutation needs further studies to find out the therapeutic approaches for CD
treatment.
References:
1. Y. Ogura et al., Nod2, a Nod1/Apaf-1 family member that is restricted to
monocytes and activates NFκB. JBC 276, 4812-4818 (2001)
2. N. Inohara et al., Host recognition of bacterial muramyl dipeptide mediated
through NOD2. JBC 278, 5509-5512 (2003)
3. S. Maeda et al., Nod2 mutation in Crohn’s disease potentiates NFκB activity and
IL-1β processing. Science 307, 734-738 (2005)