A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation

Wu, S. Julia; Niknafs, Yashar S.; Kim, Stephanie H.; Oravecz-Wilson, Katherine; Zajac, Cynthia; Toubai, Tomomi; Sun, Yaping; Prasad, J.K.; Peltier, Daniel; Fujiwara, Hideaki; Hedig, Israel; Mathewson, Nathan D.; Khoriaty, Rami; Ginsburg, David; Reddy, Pavan

doi:10.1016/j.celrep.2017.06.013

Cited by 43 publications

(36 citation statements)

References 38 publications

(90 reference statements)

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“…Total RNA from single-cell suspensions or snap-frozen skin, liver, colon or ileum was isolated using the miRNeasy Kit (Qiagen) and reverse transcribed into cDNA using the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA). The following primers and PowerUP SYBR green polymerase (Applied Biosystems) were used to detect the following transcripts: 5′-CACGGCCTACATCCTCATCT-3′ and 5′-TTGGTAGGTACCAGCGGAAG-3′ ( Gpr43 ); 5′-CTGGCGGAGCTACGTGCT-3′ and 5′-GGGGTCGATACAAGAGT-3′ ( Gpr41 ) 43 ; 5′-ATGGCGAGGCATATCTGTGTAGCA-3′ and 5′-TCCTGCCTGAGCAGAACAAGATGA-3′ ( Gpr109a ) 44 ; 5′-GTCAACCGCACCTTTATGCT-3′ and 5′-GAACAGTTTCTCCCCGATGA-3′ ( IL-22 ); and 5′-TGACCTCAACTACATGGTCTACA-3′ and 5′-CTTCCCATTCTCGGCCTTG-3′ ( Gapdh ) 45 . All reactions were performed according to manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Microbial metabolite sensor GPR43 controls severity of experimental GVHD

et al. 2018

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Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant murine models. GPR43 is critical for the protective effects of short-chain fatty acids (SCFAs), butyrate and propionate. Increased severity of GVHD in the absence of GPR43 is not due to baseline differences in the endogenous microbiota of the hosts. We confirm the ability of microbiome-derived metabolites to reduce GVHD by several methods, including co-housing, antibiotic treatment, and administration of exogenous SCFAs. The GVHD protective effect of SCFAs requires GPR43-mediated ERK phosphorylation and activation of the NLRP3 inflammasome in non-hematopoietic target tissues of the host. These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells.

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Section: Methodsmentioning

confidence: 99%

Microbial metabolite sensor GPR43 controls severity of experimental GVHD

et al. 2018

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“…25,38,43,51,130,182,221 and FIGURE 5). Although controversial (212,333), Sec22b regulates trafficking from the ERGIC to phagosomes in dendritic cells (8,41,51). Sec22b might also be responsible for transport from the ER to phagosomes by complexing with Stx18 (Qa) and Use1 (Qc) (25,130), although this is also debated (136,267,304).…”

Section: A Sec22bmentioning

confidence: 99%

Endosomal and Phagosomal SNAREs

Dingjan

Linders

Verboogen

et al. 2018

Physiological Reviews

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The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking. Of the 38 SNAREs present in humans, 30 have been identified at endosomes and/or phagosomes. Many of these SNAREs are targeted by viruses and intracellular pathogens, which thereby reroute intracellular transport for gaining access to nutrients, preventing their degradation, and avoiding their detection by the immune system. A fascinating picture is emerging of a complex transport network with multiple SNAREs being involved in consecutive trafficking routes.

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“…Recent studies suggest that the active translocation of ERGIC-associated proteins to the phagosome via a Sec22b-mediated mechanism is required for cross-presentation. It is believed that Sec22b functions by both promoting phagosome-to-cytosol escape of the cargo, as well as inhibiting phagosomal-lysosomal maturation (Cebrian et al, 2011; Wu et al, 2017). Rubcn +/+ and Rubcn -/- DCs displayed equivalent localization of Sec22b with the ERGIC marker, Calreticulin, at a resting state (Figure 2E, Figure S3D).…”

Section: Resultsmentioning

confidence: 99%

Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

Zhao

et al. 2019

Preprint

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41Major Histocompatibility Complex I (MHC-I) molecules classically present peptides derived from 42 endogenous antigens, but exogenous antigens can also gain access to the MHC-I machinery in 43 dendritic cells (DCs), which can activate antigen-specific CD8 + T cells. This process, termed 44 cross-presentation, can be triggered by the uptake of dying autologous cells, including tumor cells, 45by DCs. The molecular mechanisms that underlie efficient cross-presentation remain largely 46 uncharacterized, and an improved understanding of these mechanisms might reveal novel 47 strategies for anti-tumor therapies. Rubicon (RUBCN) is a molecule required for LC3-associated 48 phagocytosis (LAP), but dispensable for canonical autophagy, and mice lacking this protein 49 develop an autoimmune inflammatory pathology with age. Here, we demonstrate that Rubcn-50 deficient DCs have increased retention of engulfed cellular cargo in immature phagosomes 51 resulting in increased phagosome-to-cytosol escape and antigen access to proteasome-mediated 52 degradation. As a result, mice selectively lacking Rubcn in DCs mount stronger tumor antigen-53 specific CD8 + T cell responses and exhibit decreased tumor burden compared to wild type 54 littermates. These findings identify LAP as a key regulator of cross-presentation and suggest that 55 targeting RUBCN might represent a novel strategy for anti-tumor therapy.The ability of the immune system to distinguish between self and non-self is integral to maintaining 75 homeostasis and eradicating exogenous threats. Antigen-presenting cells (APCs), specifically 76 DCs, educate the host's adaptive immune response in a controlled and antigen-specific manner. 77CD8 + T cells are activated by peptides generated from intracellular antigens and presented in the 78 context of MHC-I. Peptides derived from healthy self-antigens presented to CD8 + T cells in the 79 periphery elicit a minimal or absent response, as CD8 + T cells expressing T cell receptors (TCRs) 80 that recognize self-antigens undergo negative selection in the thymus prior to their population of 81 the periphery (Rock et al., 2016). However, when cells are infected by virus or are transformed 82 by an oncogene, they can produce proteins that are not considered self, such as virus-encoded 83 proteins, and the presentation of these aberrant antigens via MHC-I activates a robust CD8 + T 84 cell response (Hansen and Bouvier, 2009). Therefore, the MHC-I pathway represents an 85 evolutionarily conserved mechanism that serves as a quality control mechanism for endogenous 86 proteins and viral defense (Kaufman, 2018). 88As the activation of CD8 + T cells is largely limited to their localization within secondary lymphoid 89 tissues, they must rely on the migration of patrolling APCs to deliver antigens to them (Hansen 90 and Bouvier, 2009). Classically, exogenous antigens are sensed as foreign, phagocytosed, 91 processed by the endosomal-lysosomal network, and loaded onto MHC-II molecules to stimulate 92 antigen-specific activation of CD4 + T cel...

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A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation

Cited by 43 publications

References 38 publications

Microbial metabolite sensor GPR43 controls severity of experimental GVHD

Microbial metabolite sensor GPR43 controls severity of experimental GVHD

Endosomal and Phagosomal SNAREs

Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

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