NOD2 regulates hematopoietic cell function during graft-versus-host disease

Penack, Olaf; Smith, Odette M.; Cunningham‐Bussel, Amy; Liu, Xin; Rao, Uttam K.; Yim, Nury; Na, Il‐Kang; Holland, Aliya; Ghosh, Arnab; Lu, Sydney X.; Jenq, Robert R.; Liu, Chen; Murphy, Gëorge F.; Brandl, Katharina; Brink, Marcel R.M. van den

doi:10.1084/jem.20090623

Cited by 98 publications

(78 citation statements)

References 30 publications

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“…Preliminary results suggested a scaffold role for Nod2 in the pathway leading to c-Rel-mediated IL-2 transcription in response to CD28 costimulation. These findings are conflicting with previous studies showing that Nod2 is not required in generating effective Ag-specific responses after immunization with other agonists than MDP [68,78] or with data demonstrating no T cell-intrinsic role for Nod2 [84]. This intringing study will likely generate further research on Nod2 behaviour in T cells.…”

Section: Role Of Nod2 In Adaptative Immune Responsecontrasting

confidence: 66%

The protein Nod2: An innate receptor more complex than previously assumed

Lecat

Piette

Legrand-Poels

2010

Biochemical Pharmacology

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Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list.For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions.Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the 'Q' link to go to the location in the proof. Location inQuery / Remark: click on the Q link to go article Please insert your reply or correction at the corresponding line in the proof Q1If there are fewer than seven authors, please supply all their names; if there are seven or more authors, please supply the first six authors' names, followed by 'et al.'Thank you for your assistance. Graphical AbstractBiochemical Pharmacology xxx (2010) xxx-xxx pp: xxx-xxx The protein Nod2: An innate receptor more complex than previously assumed

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Section: Role Of Nod2 In Adaptative Immune Responsecontrasting

confidence: 66%

The protein Nod2: An innate receptor more complex than previously assumed

Lecat

Piette

Legrand-Poels

2010

Biochemical Pharmacology

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“…75 This was also corroborated by our group in an experimental allo-HCT model where NOD2-deficient mice showed increased GVHD and intestinal inflammation. 76 …”

Section: The Intestinal Microbiota and Gvhdmentioning

confidence: 99%

The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease

Staffas

Silva

Brink

2017

Blood

174

131

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Hematopoietic cell transplantation (HCT) is a critical treatment of patients with high-risk hematopoietic malignancies, hematological deficiencies, and other immune diseases. In allogeneic HCT (allo-HCT), donor-derived T cells recognize host tissues as foreign, causing graft-versus-host disease (GVHD) which is a main contributor to morbidity and mortality. The intestine is one of the organs most severely affected by GVHD and research has recently highlighted the importance of bacteria, particularly the gut microbiota, in HCT outcome and in GVHD development. Loss of intestinal bacterial diversity is common during the course of HCT and is associated with GVHD development and treatment with broad-spectrum antibiotics. Loss of intestinal diversity and outgrowth of opportunistic pathogens belonging to the phylum Proteobacteria and Enterococcus genus have also been linked to increased treatment-related mortality including GVHD, infections, and organ failure after allo-HCT. Experimental studies in allo-HCT animal models have shown some promising results for prebiotic and probiotic strategies as prophylaxis or treatment of GVHD. Continuous research will be important to define the relation of cause and effect for these associations between microbiota features and HCT outcomes. Importantly, studies focused on geographic and cultural differences in intestinal microbiota are necessary to define applicability of new strategies targeting the intestinal microbiota.

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“…Unlike apparent gain-of-function NOD2 mutations associated with Blau syndrome or early onset sarcoidosis, CD-associated mutations in the NOD2 gene seem to be loss-of-function, which may likely alter host-microbe interactions through various mechanisms (13). Several studies have attempted to recapitulate CD-like intestinal inflammation using chemical inducers (such as DSS or TNBS) or adoptive transfer of hematopoietic cells in mice with Nod2 null or frame-shift mutations (14,(40)(41)(42)(43). Despite many interesting observations, these mouse models were limited due to the fact that inflammation was induced mainly in the colon, whereas in CD, NOD2 mutations are mostly associated with ileal inflammation (25).…”

Section: Discussionmentioning

confidence: 99%

Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

Biswas

Liu

Hao

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

152

140

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Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn’s disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2 -deficient mice inoculated with Helicobacter hepaticus , an opportunistic pathogenic bacterium, developed granulomatous inflammation of the ileum, characterized by an increased expression of Th1-related genes and inflammatory cytokines. The Peyer’s patches and mesenteric lymph nodes were markedly enlarged with expansion of IFN-γ–producing CD4 and CD8 T cells. Rip2 -deficient mice exhibited a similar phenotype, suggesting that Nod2 function likely depends on the Rip2 kinase in this model. Transferring wild-type bone marrow cells into irradiated Nod2 -deficient mice did not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2 -deficient mice by transgenic expression of α-defensin in Paneth cells rescued the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts is critical for protecting mice from a Th1-driven granulomatous inflammation in the ileum. The model may provide insight into Nod2 function relevant to inflammation of ileal Crohn’s disease.

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NOD2 regulates hematopoietic cell function during graft-versus-host disease

Cited by 98 publications

References 30 publications

The protein Nod2: An innate receptor more complex than previously assumed

The protein Nod2: An innate receptor more complex than previously assumed

The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease

Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

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