Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Cruz, D.G. da; Giri, Raghavendra R; Turro, Daylin Gamiotea; Balsbaugh, Jeremy L.; Adler, Adam J.; Rodríguez, Annabelle

doi:10.4049/jimmunol.2001188

Cited by 17 publications

(11 citation statements)

References 47 publications

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“…We have also recently reported that bone marrow–derived dendritic cells lacking LAG3 showed enhanced antigen-induced CD4 + T cell activation and proliferation, strongly suggesting that LAG3 in non–T cells significantly influences T cell function. 27 …”

Section: Discussionmentioning

confidence: 99%

LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice

Mulholland¹,

Kritikou²,

Katra³

et al. 2022

JACC: CardioOncology

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Section: Discussionmentioning

confidence: 99%

LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice

Mulholland¹,

Kritikou²,

Katra³

et al. 2022

JACC: CardioOncology

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“…LAG-3 is also involved in DC immune suppression. LAG-3 deficiency has led to increased TNFα secretion and upregulation of glycolysis in murine bone marrow derived DC ( 111 ).…”

Section: Overcoming Strategies To Tackle DC Impairments In the Tmementioning

confidence: 99%

Strategies to overcome DC dysregulation in the tumor microenvironment

2022

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Dendritic cells (DCs) play a key role to modulate anti-cancer immunity in the tumor microenvironment (TME). They link innate to adaptive immunity by processing and presenting tumor antigens to T cells thereby initiating an anti-tumor response. However, subsets of DCs also induce immune-tolerance, leading to tumor immune escape. In this regard, the TME plays a major role in adversely affecting DC function. Better understanding of DC impairment mechanisms in the TME will lead to more efficient DC-targeting immunotherapy. Here, we review the different subtypes and functions of DCs in the TME, including conventional DCs, plasmacytoid DC and the newly proposed subset, mregDC. We further focus on how cancer cells modulate DCs to escape from the host’s immune-surveillance. Immune checkpoint expression, small molecule mediators, metabolites, deprivation of pro-immunogenic and release of pro-tumorigenic cytokine secretion by tumors and tumor-attracted immuno-suppressive cells inhibit DC differentiation and function. Finally, we discuss the impact of established therapies on DCs, such as immune checkpoint blockade. Creative DC-targeted therapeutic strategies will be highlighted, including cancer vaccines and cell-based therapies.

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“…Initial analyses of LAG3 expression in dendritic cell (DC) subsets showed high LAG3 expression by plasmacytoid but not lymphoid or myeloid conventional DCs 7 . However, a more recent study demonstrated a role for LAG3 on bone marrow derived DCs in optimal T cell priming 51 . Due to these controversies, the impact of LAG3 deficiency in recipient APCs needs to be carefully dissected in future studies.…”

Section: Discussionmentioning

confidence: 99%

LAG3 regulates antibody responses in a murine model of kidney transplantation

Nicosia

Fan

Lee

et al. 2022

Preprint

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Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by a wide range of immune cells. While LAG3 is predominantly studied in T cells, its functions in humoral immune responses remain poorly characterized. The goal of this study was to test the role of recipient LAG3 in a mouse model of renal allograft rejection. Compared to WT animals, naïve B6.LAG3-/- mice have increased splenic cellularity and higher frequencies of CD44hi memory T cells, CXCR5hi follicular T cells, and B220+CD138+ plasma cells yet do not develop spontaneous autoimmunity. Furthermore, naïve B6.LAG3-/- (H-2Db) mice have increased frequencies of memory T cells recognizing H-2Dd, H-2Ds, H-2Dq and H-2Dk alloantigens. In addition, naïve non-transplanted B6.LAG3-/- mice have elevated levels of serum IgG reactive to allogenic class I and class II MHC molecules. Whereas 4/4 B6.WT recipients spontaneously accept fully MHC-mismatched C3H (H-2k) renal allografts for longer than 60 d, recipient LAG3 deficiency led to rapid allograft rejection and elevated serum creatinine levels. Graft histology at rejection revealed minimal T cell infiltration, diffuse C4d staining, atrophic peritubular capillaries, endothelial swelling and edema characteristic of antibody mediated rejection (AMR). Compared to WT, LAG3-/- recipients had elevated frequencies of anti-donor IFNγ producing T cells and increased levels of anti-donor MHC antibodies. Recipient CD8+ T cell depletion did not alter the rejection kinetics in LAG3-/- recipients, while B cell depletion significantly extended C3H kidney allograft survival. Conditional knockout mice were used to determine the importance of LAG3 expression by T and B lymphocytes. The absence of LAG3 on either T or B lymphocytes had no impact on graft rejection with both groups accepting kidney allografts for longer than 30 days, suggesting that LAG3 expression on either T or B cells is sufficient to regulate immune responses to kidney allografts. These results suggest that LAG3 is a regulator of both T and B cell responses to kidney allografts and is an attractive potential therapeutic target for AMR prevention and treatment.

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Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Cited by 17 publications

References 47 publications

LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice

LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice

Strategies to overcome DC dysregulation in the tumor microenvironment

LAG3 regulates antibody responses in a murine model of kidney transplantation

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