Loss of a gimap/ian gene leads to activation of NF-κB through a MAPK-dependent pathway

Kupfer, René; Lang, Julie; Williams-Skipp, Cheryll; Nelson, Matt; Bellgrau, Donald; Scheinman, Robert I.

doi:10.1016/j.molimm.2006.02.014

Cited by 17 publications

(16 citation statements)

References 38 publications

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“…40 Moreover, gimap5-mediated regulation of T-cell survival and quiescence may involve mitogen-activated protein kinase kinase (MEK)-dependent activation of the upstream regulator of NF-B, IB kinase (IKK). 41 Together, these observations raise the possibility that gimap5 interacts in a critical manner with the NF-B signaling pathway. The reported role of NF-B in the differentiation of marginal zone B cells 42 prompted us to examine in detail B-cell differentiation in Gimap5 Ϫ/Ϫ mice, and preliminary results show indeed a severe deficiency of both marginal zone B cells in the spleen, and B1 peritoneal B cells (our unpublished observations, August 2008).…”

Section: Discussionmentioning

confidence: 95%

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis

Chu

Dai

et al. 2008

Blood

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Section: Discussionmentioning

confidence: 95%

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis

Chu

Dai

et al. 2008

Blood

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“…on April 27, 2019. by guest www.bloodjournal.org From regulated developmentally by engagement of the ␣␤TCR at positive selection, 25,26 and from their up-regulation of CD40L in vitro in response to stimulation through the TCR with the anti-CD3 antibody 27 (with or without anti-CD28 costimulation; supplemental Figure 1B) both of which were equivalent to wild-type controls.…”

Section: Gimap1 Is Required For Lymphocyte Development 3251mentioning

confidence: 90%

“…The mechanism by which GIMAP5 promotes T-lymphocyte survival has been the subject of diverse proposals, 1,26,[34][35][36][37] including hypotheses relating to mitochondrial permeability, mitogenactivated protein kinase and nuclear factor B (NF-B) signaling, interaction with Bcl-2 family members, regulation of calcium signaling and the endoplasmic reticulum stress pathway. A weakness intrinsic to a number of these conclusions is their basis in data from the GIMAP5-mutant rat, in which the few residual peripheral T cells are intrinsically short-lived and of unusual phenotype.…”

Section: Discussionmentioning

confidence: 99%

Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Saunders¹,

Webb²,

Janas³

et al. 2010

Blood

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“…Thymic development in the BB-DP rat is largely normal, but peripheral CD4+ T cells are reduced in number and peripheral CD8+ T cells are virtually absent. Moreover, the phenotype of surviving peripheral T cells indicates they are recent thymic emigrants (RTE), so death must occur rapidly after thymocytes enter the periphery (51,62,63). On the other hand, the Ian5 knockout mouse shows compromised survival of both peripheral T cells and double positive thymocytes (60).…”

Section: Ian5 In Negative Regulation and Survivalmentioning

confidence: 99%

“…T cells from Ian5-deficient rats spontaneously enter this state of partial or incomplete activation, and this is not simply a response to the lymphopenic environment, but rather it is due to elevated activity of MEK that in turn leads to constitutive activation of NFκB. Moreover, the phenotype is intrinsic to the T cells, as it occurs in bone marrow chimeras where Ian5 mutant T cells develop in a wild type environment (51). Thus, partial T cell activation in Ian5-deficient animals is not a consequence of lymphopenia but is rather part of the stimulus leading to cell death, providing one biochemical link between survival and quiescence pathways (42,51).…”

Section: Ian5 In Negative Regulation and Survivalmentioning

confidence: 99%

Negative regulators in homeostasis of naïve peripheral T cells

2008

Self Cite

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It is now apparent that naïve peripheral T cells are a dynamic population where active processes prevent inappropriate activation while supporting survival. The process of thymic education makes naïve peripheral T cells dependent on interactions with self-MHC for survival. However, as these signals can potentially result in inappropriate activation, various non-redundant, intrinsic negative regulatory molecules including Tob, Nfatc2, and Smad3 actively enforce T cell quiescence. Interactions among these pathways are only now coming to light and may include positive or negative crosstalk. In the case of positive crosstalk, self-MHC initiated signals and intrinsic negative regulatory factors may cooperate to dampen T cell activation and sustain peripheral tolerance in a binary fashion (on-off). In the case of negative crosstalk, self-MHC signals may promote survival through partial activation while intrinsic negative regulatory factors act as rheostats to restrain cell cycle entry and prevent T cells from crossing a threshold that would break tolerance. KeywordsT cells; MHC; sensitization; desensitization; cell cycle; negative regulation; tolerance The Influence of Self-MHC in T-Cell Quiescence and Survival Self-MHC and naïve T cell survivalThe role of self-peptides complexed to major histocompatibility complex proteins (self-MHC) to maintain homeostasis of naïve T cells has been the subject of extensive investigation over the past decade. This work has revealed apparent differences in the sensitivity of different T cell subsets to the absence of self-MHC. Perhaps the most informative experiments have attempted to characterize the expansion of peripheral lymphocytes in MHC-replete or MHCdeficient lymphopenic environments. The idea that "space" in the peripheral lymphoid organs drove lymphocyte proliferation arose from the observation that under conditions of lymphopenia such as those produced by non-myeloablative, lymphodepleting regimens in humans or mice, or under conditions encountered by adoptively transferred lymphocytes or bone marrow cells into lymphopenic hosts, T cells would expand without exogenous antigens. It is now apparent that this "lymphopenia-induced proliferation" or "homeostatic proliferation" (HP) results not only from "space", but also from interactions of T cell receptors (TCR) with self-MHC, and from lessened competition for cytokines including interleukin-7 (IL-7), or in some cases, Unlike HP in MHC-replete hosts, a majority of naïve T cells die or make at most a few divisions if the lymphopenic periphery is devoid of MHC (16-21), a result consistent with the premise that HP is itself partly driven by recognition of self-MHC complexes. Both CD4 and CD8 T cells undergo HP, although CD4 T cells expand less in response to MHC and CD8 T cells are more sensitive to its absence. In fact, while the requirement for self-MHC in naïve CD8 T cell survival is generally accepted (although it may not apply to all CD8 T cell subsets) (22), the delayed erosion of naïve CD4 T cells in lymphopenic h...

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Loss of a gimap/ian gene leads to activation of NF-κB through a MAPK-dependent pathway

Cited by 17 publications

References 38 publications

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Negative regulators in homeostasis of naïve peripheral T cells

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