Exogenous Heat Shock Protein gp96 Ameliorates CD4+CD62L+ T-Cell–mediated Transfer Colitis

Fischbeck, Anne; Schreiter, K.; Leucht, Katharina; Frey-Wagner, Isabelle; Lang, Silvia; Hausmann, Martin; Fried, Michael; Falk, Werner; Rogler, Gerhard

doi:10.1097/mib.0000000000000175

Cited by 1 publication

(2 citation statements)

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“…This theory is supported by the fact that gp96 is induced during differentiation of normal intestinal macrophages, but not detected in intestinal macrophages in the gut mucosa of CD patients [134]. As gp96 may have a role in tolerance induction, this observation suggests that downregulation of gp96 is responsible for the loss of tolerance against luminal bacteria found in CD patients [134, 135]. …”

Section: Role Of Gp96 In Cancermentioning

confidence: 99%

“…They further demonstrated that immunization with high doses of gp96 can prevent myelin basic protein- or proteolipid protein-induced autoimmune encephalomyelitis in SJL mice and the onset of diabetes in non-obese diabetic (NOD) mice [148]. Similar protective effects were implicated in T cell-mediated immune disorders including IBD [135] and liver injury [149]. These studies indicated that gp96 plays different immune regulatory roles in a dose-dependent manner.…”

Section: T Cell Intrinsic Gp96: Implications For Cellular Therapymentioning

confidence: 99%

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Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94

Ansa-Addo¹,

Thaxton²,

Hong³

et al. 2016

CTMC

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As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt co-receptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF). Clinically, elevated expression of gp96 in a variety of cancers correlates with the advanced stage and poor survival of cancer patients. Recent preclinical studies have also uncovered that gp96 expression is closely linked to cancer progression in multiple myeloma, hepatocellular carcinoma, breast cancer and inflammation-associated colon cancer. Thus, gp96 is an attractive therapeutic target for cancer treatment. The chaperone function of gp96 depends on its ATPase domain, which is structurally distinct from other HSP90 members, and thus favors the design of highly selective gp96-targeted inhibitors against cancer. We herein discuss the strategically important oncogenic clients of gp96 and their underlying biology. The roles of cell-intrinsic gp96 in T cell biology are also discussed, in part because it offers another opportunity of cancer therapy by manipulating levels of gp96 in T cells to enhance host immune defense.

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Section: Role Of Gp96 In Cancermentioning

confidence: 99%