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Crohn's Disease Forum » Books, Multimedia, Research & News » Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature


07-29-2013, 11:33 PM   #1
kiny
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Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature






07-30-2013, 01:35 AM   #2
rollinstone
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I didn't read the whole thing coz it was confusing can you put it in laments terms for me Kin?
07-30-2013, 04:03 PM   #3
kiny
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Another study explained it better. The above is more of an overview tbh.

" Autophagy is used to degrade micro-organisms that invade intracellularly in a process termed xenophagy. Genome-wide association scans have recently identified autophagy genes as conferring susceptibility to Crohn’s disease (CD), one of the chronic inflammatory bowel diseases, with evidence suggesting that CD arises from a defective innate immune response to enteric bacteria. Here we review the emerging role of autophagy in CD, with particular focus on xenophagy and enteric E. coli strains with an adherent and invasive phenotype that have been consistently isolated from CD patients with ileal disease."
07-30-2013, 10:22 PM   #4
JaneInTheRain
 
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I really appreciate all the studies you post
07-30-2013, 10:43 PM   #5
kiny
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thankies
03-23-2016, 08:40 AM   #6
xeridea
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A new study in this realm. This time, they're looking at another condition, called Niemann-Pick disease, and linking genetic defects there that lead to severe Crohn's in this patient group.

If their theory holds up in further research, it opens possibility of having drugs that upregulate autophagy available to treat Crohn's.

Impaired bacterial clearance in IBD

Patients with the neurodegenerative lysosomal lipid storage disorder Niemann-Pick disease typeC1 (NPC1) can present with IBD, but the functional mechanism of this association was previously unclear.

New findings now shed light on this link, showing that impaired induction of autophagy resulting in defective clearance of bacteria underlies intestinal inflammation in patients with NPC1 and other genetic defects, pinpointing a potential new therapeutic target. Polygenic IBD, in particular Crohn’s disease, is associated with many genetic variants that affect bacterial clearance and autophagy. The stongest risk factor for Crohn’s disease is mutations in NOD2, which is important for bacterial muramyl peptide sensing. Additionally, a number of rare monogenic disorders can also present with Crohn’s disease, one of which is deficiency in XIAP, an essential signal transducer downstream of NOD2. As Crohn’s disease and XIAP deficiency share a common pathway and phenotype, the researchers chose to investigate patients with NPC1, another monogenic disorder that presents with intestinal inflammation.

“We think that understanding monogenic disorders with genetic defects that have high functional impact will allow us to better define key modules in the immune system that confer susceptibility to IBD in general,” explains author HolmUhlig.

Patients with NCP1 can develop granulomatous colitis, which is indicative of ineffective clearance of gut microbiota by macrophages. Thus, bacterial handling was characterized in macrophages derived from patients with NCP1 who had severe Crohn’s-diseaselike intestinal inflammation with evidence of granuloma, and compared with functional defects caused by NOD2 or XIAP mutations. Using an invitro assay of bacterial clearance, bacterial handling was first shown to be defective in NOD2-associated and XIAP-associated Crohn’s disease, caused by impaired initiation of autophagy.

Defective elimination of intracellular bacteria was then demonstrated in macrophages from patients with NCP1, which was also attributed to dysfunctional autophagy but at a critical stage of autophagosome maturation between bacterial sensing and degradation.

Furthermore, pharmacological induction of autophagy was shown to restore autophagic flux and rescue invitro bacterial handling inNPC1macrophages.

“We think this is a very exciting finding since it links the NCP1 defect in the endosomal and lysosomal compartment with defective cytoplasmic bacterial recognition by NOD2 and signalling via XIAP. Our findings add to the concept that common and rare genetic variation in shared cellular pathways leads to shared phenotypes,” says Uhlig. The effects of these heterogenous genetic defects highlight bacterial clearance as an important factor in Crohn’s disease and suggest that therapeutic modification of elimination mechanisms could be a promising treatment option forIBD.

The researchers plan to investigate how other gene defects that cause Crohn’s disease might affect bacterial handling and will test whether autophagy inducers can rescue immune defects in patients.
03-27-2016, 03:38 PM   #7
Malgrave
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Here is a link to the full paper:

http://gut.bmj.com/content/early/201...10382.full.pdf
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