A cyclophilin-related protein involved in the function of natural killer cells.

Anderson, Stephen; Gallinger, Steven; Roder, John; Frey, Joyce L.; Young, Howard A.; Ortaldo, John R.

doi:10.1073/pnas.90.2.542

Cited by 106 publications

(63 citation statements)

References 37 publications

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“…RTN4 is a potent neurite outgrowth inhibitor and plays a role in autoimmune demyelination (29). NKTR is highly expressed on the surface of natural killer cells where it facilitates tumor cell recognition by a MHC-independent pathway (30). Expression of NKTR on the surface of glioma cells may interfere with tumor cell recognition.…”

Section: Discussionmentioning

confidence: 99%

Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Ludwig¹,

Keller

Comtesse³

et al. 2008

Clinical Cancer Research

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Purpose: Recent studies impressively showed the diagnostic potential of seroreactivity patterns for different tumor types, offering the prospect for low-cost screening of numerous tumor types simultaneously. One of the major challenges toward this goal is to prove that seroreactivity profiles do not only allow for identifying a tumor but also allow for distinguishing tumors from other pathologies of the same organ. Experimental Design: We chose glioma as a model system and tested 325 sera (88 glioma, 95 intracranial tumors, 60 other brain pathologies, and 82 healthy controls) for seroreactivity on a panel of 35 antigens. Results: We were able to discriminate between glioma and all other sera with cross-validated specificity of 86.1%, sensitivity of 85.2%, and accuracy of 85.8%.We obtained comparably good results for the separation of glioma versus nontumor brain pathologies and glioma versus other intracranial tumors. Conclusion: Our study provides first evidence that seroreactivity patterns allow for an accurate discrimination between a tumor and pathologies of the same organ even between different tumor types of the same organ.

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Section: Discussionmentioning

confidence: 99%

Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Ludwig¹,

Keller

Comtesse³

et al. 2008

Clinical Cancer Research

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“…However, several multidomain cyclophilins from different organisms have been described as well. These include Ess1/Pin1 (Hanes et al 1989;Lu et al 1996), TLP40 (Fulgosi et al 1998), hCyP33 (Mi et al 1996), CyP-13 (Zorio and Blumenthal 1999), SRcyp (Bourquin et al 1997), mocaCYP (Cavarec et al 2002), NK-TR1 (Anderson et al 1993;Rinfret et al 1994), CypRS64 and CypRS92 (Lorković et al 2004b), and Kin241p (Krzywicka et al 2001), the last eight having domains characteristic for nuclear proteins being involved in premRNA maturation. SRcyp, mocaCYP, NK-TR1, CypRS64, and CypRS92 are highly similar nuclear proteins consisting of an N-terminal PPIase domain followed by a charged domain and a C-terminal domain rich in arginine/serine (RS) dipeptides that are characteristic for splicing factors called SR proteins (Graveley 2000;Sanford et al 2003).…”

Section: Introductionmentioning

confidence: 99%

AtCyp59 is a multidomain cyclophilin from Arabidopsis thaliana that interacts with SR proteins and the C-terminal domain of the RNA polymerase II

Gullerová¹,

Barta²,

Lorković³

2006

RNA

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AtCyp59 and its orthologs from different organisms belong to a family of modular proteins consisting of a peptidyl-prolyl cistrans isomerase (PPIase) domain, followed by an RNA recognition motif (RRM), and a C-terminal domain enriched in charged amino acids. AtCyp59 was identified in a yeast two-hybrid screen as an interacting partner of the Arabidopsis SR protein SCL33/ SR33. The interaction with SCL33/SR33 and with a majority of Arabidopsis SR proteins was confirmed by in vitro pull-down assays. Consistent with these interactions, AtCyp59 localizes to the cell nucleus, but it does not significantly colocalize with SR proteins in nuclear speckles. Rather, it shows a punctuate localization pattern resembling transcription sites. Indeed, by using yeast two-hybrid, in vitro pull-down, and immunoprecipitation assays, we found that AtCyp59 interacts with the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Ectopic expression of the tagged protein in Arabidopsis cell suspension resulted in highly reduced growth that is most probably due to reduced phosphorylation of the CTD. Together our data suggest a possible function of AtCyp59 in activities connecting transcription and pre-mRNA processing. We discuss our data in the context of a dynamic interplay between transcription and pre-mRNA processing.

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“…The chemokines responsible for directing leukocyte migration during immune homeostasis and inflammation are well characterized (11,12,17,18), but there is a general lack of information regarding the role of chemokines and cell trafficking during the induction of peripheral tolerance. Previously, we showed that during the induction of tolerance to Ags injected into the eye, eyederived APCs selectively increased expression of macrophage-inflammatory protein (MIP) 3 -2 during their preferential migration to the splenic marginal zones (MZ) and that MIP-2 was responsible for recruiting NKT cells to the spleen (19).…”

mentioning

confidence: 99%

NKT Cell-Derived RANTES Recruits APCs and CD8+ T Cells to the Spleen During the Generation of Regulatory T Cells in Tolerance

Faunce

Stein‐Streilein

2002

The Journal of Immunology

118

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The induction of peripheral tolerance via immune privileged sites such as the eye requires splenic colocalization of NKT cells and CD1d+ tolerogenic F4/80+ APCs, both of which are needed for the generation of CD8+-regulatory T (Tr) cells. Whereas tolerogenic APCs secrete the chemokine macrophage-inflammatory protein-2 for the purpose of recruiting NKT cells, the signals responsible for recruiting potential Tr cells and additional APCs to the spleen are not known. Here we examined the ability of CD1d-stimulated NKT cells to produce chemokines that can recruit other cells needed for tolerance. Our results show that NKT cells stimulated by either CD1d-transfected fibroblasts in vitro or CD1d+ tolerogenic APCs both in vivo and ex vivo produced RANTES in a CD1d-dependent manner. The requirement for RANTES in tolerance was demonstrated by studies in which RANTES blockade in vivo prevented not only APC accumulation in the spleen but also the generation of CD8+ Tr cells that suppress Th1 immunity. Thus, CD1d-restricted NKT cells provide critical signals for orchestrating the accumulation of cells needed for tolerance induction. These data expand our current knowledge of RANTES beyond its role in Th1 immune responses to show its importance in tolerance induction and add a novel aspect to our understanding of the role of NKT cells in tolerance. Understanding the precise mechanisms involved in tolerance induction may lead to more effective therapeutic strategies for autoimmunity and graft rejection.

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A cyclophilin-related protein involved in the function of natural killer cells.

Cited by 106 publications

References 37 publications

Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

AtCyp59 is a multidomain cyclophilin from Arabidopsis thaliana that interacts with SR proteins and the C-terminal domain of the RNA polymerase II

NKT Cell-Derived RANTES Recruits APCs and CD8+ T Cells to the Spleen During the Generation of Regulatory T Cells in Tolerance

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