Peritoneal macrophages suppress T‐cell activation by amino acid catabolism

Matlack, Robin; Yeh, K.; Rosini, L.; Gonzalez, Diana; Taylor, Justin J.; Silberman, Daniel; Pennello, Anthony L.; Riggs, James E.

doi:10.1111/j.1365-2567.2005.02312.x

Cited by 28 publications

(61 citation statements)

References 56 publications

(170 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kupffer cells (KCs), resident liver macrophages, are long lived and abundant, representing 15 to 20% of the total liver cell population (42,68). Resting KCs, one of the first types of immune cells to be exposed to materials absorbed in the gut, contribute to the generally tolerogenic environment in the liver (3,41,68,77,86), including suppression of T-cell activation (51). Nevertheless, during immune responses, KCs, like circulating monocytes drawn into the liver, can be activated by various stimuli (17,19,22,26,34,47,57,59,64,73,77,83) (Table 1).…”

Section: Macrophages In the Livermentioning

confidence: 99%

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Heydtmann

2009

J Virol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major health burdens worldwide, with over 300 and 170 million people, respectively, infected. HBV, a DNA virus, and HCV, an RNA virus, are both hepatotropic, and both lead to hepatitis in many patients, with potentially fatal complications, including hepatocellular carcinoma. A high proportion of HCV-and HBV-infected patients develop chronic infections characterized by absent, weak, or narrowly focused T-cell responses (70). It is likely that early immune avoidance mechanisms contribute to the disturbed T-cell responses in combination with various other strategies reviewed elsewhere (7,28,31,36,70,82). The two viruses differ considerably in their interactions with the host immune system, but all current treatment protocols aimed at clearing either virus include alpha interferon (IFN-␣). This implies that the innate immune system is of pivotal importance in the development and maintenance of chronic infection versus viral clearance.Critical components of the innate immune response are liver macrophages. Here we highlight their key roles in both the favorable and adverse responses to HBV and HCV infections.

show abstract

Section: Macrophages In the Livermentioning

confidence: 99%

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Heydtmann

2009

J Virol

View full text Add to dashboard Cite

show abstract

“…57, 2008 Regulatory T cells and macrophages 567 and resulted in degradation of tryptophan. Seven years later, Matlack and his colleagues [35] confirmed and extended this mechanism in mice. They found that through tryptophan and arginine catabolism, peritoneal macrophages inhibited T lymphocyte activation in a cell dose-dependent and MHCindependent fashion.…”

Section: Suppression Of Effector T Cells By Subsets Of Macrophagesmentioning

confidence: 64%

“…As a type of APCs, but different from DCs, macrophages may mainly mediate anergy in allogeneic T cells in humans and mice, supporting the concept that resting macrophages maintain peripheral immune tolerance in vivo [19,35]. Several studies show that macrophages are tolerogenic in tumors and inflammatory diseases [36,37].…”

Section: Suppression Of Effector T Cells By Subsets Of Macrophagesmentioning

confidence: 98%

Regulatory CD4+CD25+ T cells and macrophages: communication between two regulators of effector T cells

Zheng

Zhao

2008

Inflamm. res.

View full text Add to dashboard Cite

Regulatory T cells (Tregs) play an essential role in the induction and maintenance of peripheral tolerance as well as prevention of autoimmunity by limiting the strength of the immune response of effector T cells. Macrophages, a heterogeneous population of phagocytes and professional antigen presenting cells (APCs), can also exert suppressive effects on effector T cells to keep the peripheral balance of immunity. The bi-directional interactions of dendritic cells (DCs) and Tregs have been cell studied. However, much less is known about the reciprocal interaction between macrophages and Tregs. In this review, we will discuss recent observations regarding the interplay of these two regulators of immunity.

show abstract

“…In particular, T cells are exposed to this microenvironment as they are recruited to participate in the immune response. T cell proliferation is known to be susceptible to the effects of enzymes expressed by APCs that catabolize and lower concentrations of amino acids, such as tryptophan and arginine, in mixed leukocyte reactions (19,56). With respect to IDO1, this is in part due to an amino acid stress response since proliferation can be restored through the addition of excess tryptophan (5,19).…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Deprivation Links BLIMP-1 to the Immunomodulatory Enzyme Indoleamine 2,3-Dioxygenase

Barnes

Stephenson

Tooze

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Catabolism of tryptophan by IDO1 plays an important role in the control of immune responses. Activation of the eukaryotic initiation factor 2α (eIF2α) kinase general control nonderepressible-2 (GCN2) following tryptophan depletion is a major pathway mediating this effect. However, immunomodulatory target genes of GCN2 activation are poorly defined. The transcriptional repressor B lymphocyte-induced maturation protein-1 (BLIMP-1) is a target of the eIF2α kinase1, protein kinase-like ER kinase (PERK) during the unfolded protein response of the endoplasmic reticulum. Thus, BLIMP-1 might also be a mediator of the GCN2 stress response pathway activated by IDO1 and tryptophan depletion. Indeed, in human monocytes BLIMP-1 mRNA and protein are up-regulated in response to both a pharmacological activator of GCN2 and tryptophan-depletion generated by IDO1-transfected cells. This suggests a functional role for BLIMP-1 in the immunomodulatory effects of the IDO1-GCN2 axis. BLIMP-1 has been shown to repress IFN-γ-regulated promoters. As IDO1 is itself highly responsive to IFN-γ, we hypothesized that BLIMP-1 functions in a feedback loop to regulate IDO1 expression. We found that BLIMP-1 binds to IFN-responsive sites in the IDO1 promoter and represses IFN-dependent IDO1 activation. We propose that BLIMP-1 acts in a negative feedback loop to successfully balance the outcome of tolerance vs inflammation.

show abstract

Peritoneal macrophages suppress T‐cell activation by amino acid catabolism

Cited by 28 publications

References 56 publications

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Regulatory CD4+CD25+ T cells and macrophages: communication between two regulators of effector T cells

Amino Acid Deprivation Links BLIMP-1 to the Immunomodulatory Enzyme Indoleamine 2,3-Dioxygenase

Contact Info

Product

Resources

About