Expression of lectin-like transcript-1 in human tissues

Llibre, Alba; Garner, Lucy C.; Partridge, Amy; Freeman, Gordon J.; Klenerman, Paul; Willberg, Christian

doi:10.12688/f1000research.10009.1

Cited by 11 publications

(12 citation statements)

References 34 publications

(60 reference statements)

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“…However, some PB NK cells can express the CD161 antigen, also called NKRP1A (67, 68). This receptor is upregulated on NK cells upon stimulation with IL2 and, more importantly, it is expressed on majority of intestinal infiltrating lymphocytes (68, 69), including NK cells and some subsets of ILC (2, 5, 10). It has been demonstrated that CD161 can function as an adhesion molecule involved in the transmigration of PB CD4 + T cells through endothelial cells (70).…”

Section: Nk Cell Localization In the Gutmentioning

confidence: 99%

Human Gut-Associated Natural Killer Cells in Health and Disease

et al. 2019

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It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals and virus infections. The functions of NK cells in the gut are much more complex. Gut NK cells are not precisely organized in lymphoid aggregates but rather scattered in the epithelium or in the stroma, where they come in contact with a multitude of antigens derived from commensal or pathogenic microorganisms in addition to components of microbiota. Furthermore, NK cells in the bowel interact with several cell types, including epithelial cells, fibroblasts, macrophages, dendritic cells, and T lymphocytes, and contribute to the maintenance of immune homeostasis and development of efficient immune responses. NK cells have a key role in the response to intestinal bacterial infections, primarily through production of IFNγ, which can stimulate recruitment of additional NK cells from peripheral blood leading to amplification of the anti-bacterial immune response. Additionally, NK cells can have a role in the pathogenesis of gut autoimmune inflammatory bowel diseases (IBDs), such as Crohn's Disease and Ulcerative Colitis. These diseases are considered relevant to the generation of gastrointestinal malignancies. Indeed, the role of gut-associated NK cells in the immune response to bowel cancers is known. Thus, in the gut immune system, NK cells play a dual role, participating in both physiological and pathogenic processes. In this review, we will analyze the known functions of NK cells in the gut mucosa both in health and disease, focusing on the cross-talk among bowel microenvironment, epithelial barrier integrity, microbiota, and NK cells.

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Section: Nk Cell Localization In the Gutmentioning

confidence: 99%

Human Gut-Associated Natural Killer Cells in Health and Disease

et al. 2019

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“…Because LLT1 can be expressed on different cell and tissue types, it presents the possibility for the cancer cells to escape the immunosurveillance of NK cells [ 102 ]. We have shown that the expression of LLT1 on target tissues such as triple-negative breast cancer cells and prostate cancer cells inhibits the NK cell response ( Figure 2 ) [ 17 , 103 ].…”

Section: Nk Cell Receptorsmentioning

confidence: 99%

Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer

Buller

Mathew

2020

Cancers

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Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-γ production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell inhibitory receptor NKRP1A (CD161) and inhibits NK cytolytic function. Extensive research has been done on novel therapies that target these receptors to increase the effector function of NK cells. The 2B4 receptor is involved in the rejection of melanoma cells in mice. Empliciti, an FDA-approved monoclonal antibody, explicitly targets the CS1 receptor and enhances the NK cell cytotoxicity against multiple myeloma cells. Our studies revealed that LLT1 is expressed on prostate cancer and triple-negative breast cancer cells and allows them to evade NK-cell-mediated killing. In this review, we describe NK cell receptors 2B4, CS1, and LLT1 and their potential in targeting cancer cells for NK-cell-mediated immunotherapy. New cancer immunotherapies like chimeric antigen receptor T (CAR-T) and NK (CAR-NK) cells are showing great promise in the treatment of cancer, and CAR cells specific to these receptors would be an attractive therapeutic option.

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“…CD161 is expressed by the majority of SI PLZF + CD4 + T cells (Figure 1, D and F) and has been ascribed conflicting roles in either the activation or inhibition of human immune cells (45)(46)(47). LLT1, the natural ligand for CD161, is broadly distributed in human tissues, with the highest levels of expression in immune-privileged sites (48,49). LLT1 was expressed on the majority of intestinal CD14 + antigen-presenting cells (APCs), but not CD11c + CD14 -DCs ( Figure 7C).…”

Section: Introductionmentioning

confidence: 99%

CD161 contributes to prenatal immune suppression of IFN-γ–producing PLZF+ T cells

Halkias¹,

Rackaityte²,

Hillman³

et al. 2019

Journal of Clinical Investigation

109

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BACKGROUND. While the human fetal immune system defaults to a program of tolerance, there is a concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response, with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown. METHODS.We analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with proinflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared with that of healthy term controls. RESULTS.We identified a transcriptionally distinct population of CD4 + T cells characterized by expression of the transcription factor promyelocytic leukemia zinc finger (PLZF). PLZF + CD4 + T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced proinflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFN-γ in a fetal-specific manner. IFN-γ-producing PLZF + CD4 + T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation. CONCLUSION.Our work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies. cells in the development of protective immunity and their contribution to perinatal immune dysregulation is not known.Here, we performed a detailed analysis of human CD4 + T cell phenotype and function in fetal lymphoid and mucosal tissues. We show that Vα7.2 -PLZF + TCR-αβ + CD4 + T cells (herein referred to as PLZF + CD4 + T cells) specifically accumulated in the fetal intestine and were absent from the adult. Fetal PLZF + CD4 + T cells represent a transcriptionally unique subset of CD4 + T cells that are distinct from either innate-like, semi-invariant Va7.2 + T cells or PLZF -CD4 + T cells. Consistent with a primarily T effector memo-memory originates in utero. Innate-like T cells with rapid effector functions, such as γδ T cells, mucosa-associated invariant T (MAIT) cells, and innate-like NKT cells, are also present in fetal tissues (23)(24)(25). Promyelocytic leukemia zinc finger (PLZF), a transcriptional regulator that directs the differentiation of innate-like T cells (26,27), is widely expressed in human immune cells and is commonly associated with expression of CD161, a C-type lectin receptor (28). The human fetal thymus uniquely produces a subset of CD4 + T cells, distinct from NKT cells and MAIT cells, that expresses the transcription factor PLZF (29). However, the role of fetal PLZF ...

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Expression of lectin-like transcript-1 in human tissues

Cited by 11 publications

References 34 publications

Human Gut-Associated Natural Killer Cells in Health and Disease

Human Gut-Associated Natural Killer Cells in Health and Disease

Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer

CD161 contributes to prenatal immune suppression of IFN-γ–producing PLZF+ T cells

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