Disease relevance of LTBR

• In this study, we have shown that LT beta R is expressed in a variety of tissues and cell lines of monocytic lineage, as well as in fibroblast and human melanoma cell lines [1].
• Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor [2].
• In this study, immunohistochemical techniques were used to evaluate the expression of three receptors of this family (4-1BB, lymphotoxin-beta receptor (LTbeta-R), and Fas) in normal human lung, lung carcinomas and by tuberculous and sarcoid granulomas [3].
• Muscle atrophy and bone loss after 90 days' bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study [4].
• Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha [5].

High impact information on LTBR

• Blockade of TNFSF14 signaling caused a substantial reduction in the expression of lymphotoxin beta receptor (LTbetaR)-controlled migration factors within the islets and disrupts organization of tertiary structures, leading to prevention of diabetes [6].
• Recruitment and activation of naive T cells in the islets by lymphotoxin Beta receptor-dependent tertiary lymphoid structure [6].
• This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL [7].
• The hyperproliferative, inflammatory skin disease in K14-Cre-IKK2fl/fl mice was a direct consequence of the presence of macrophages in the skin, as targeted deletion of CD18, which prevented accumulation of granulocytes but not macrophages, did not lead to major changes in the phenotype [8].
• The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of beta2 integrins (CD11/CD18) to only 2-16% of WT levels [9].

Biological context of LTBR

• Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB [10].
• It has been shown that LIGHT triggers apoptosis of various tumor cells including HT29 cells that express both lymphotoxin beta receptor (LTbetaR) and HVEM/TR2 receptors [11].
• Because there is no enzymatic activity associated with the receptor itself, the signal transduction of LT beta R is mediated by cytoplasmic proteins recruited to receptors [12].
• Lymphotoxin-beta receptor (LTbetaR) and CD40 are members of the tumor necrosis factor family of signaling receptors that regulate cell survival or death through activation of NF-kappaB [13].
• Lymphotoxin-beta receptor (LT beta R) is a member of tumor necrosis factor receptor family and plays essential roles in the embryonic development and organization of secondary lymphoid tissues [12].

Anatomical context of LTBR

• Their association with LT beta R was further confirmed by coimmunoprecipitation in U937 cells and HEK293 cells [12].
• Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression [14].
• Moreover, blocking CD18 MHM23 antibody, cytochalasin B, and D609 (an inhibitor of phosphatidylcholine phospholipase C) inhibited this redistribution and the respiratory burst in TNF-treated neutrophils exposed to anti-PR3 or anti-MPO antibodies [15].
• LT beta expression was seen on astrocytes and oligodendrocytes, and LT beta-R on astrocytes [16].
• GA-binding protein (GABP) and Sp1 are required, along with retinoid receptors, to mediate retinoic acid responsiveness of CD18 (beta 2 leukocyte integrin): a novel mechanism of transcriptional regulation in myeloid cells [17].

Associations of LTBR with chemical compounds

• The human lymphotoxin beta receptor (LTbetaR), a member of the tumor necrosis factor (TNF) receptor superfamily, is essential for not only the development and organization of secondary lymphoid tissues, but also for chemokine release [18].
• CD18 (beta(2) leukocyte integrin) is transcriptionally regulated in myeloid cells, but the mechanisms that increase its expression in response to retinoic acid (RA) have not been defined [17].
• Serine/threonine kinase activity associated with the cytoplasmic domain of the lymphotoxin-beta receptor in HepG2 cells [19].
• For 3 of these, the corresponding cDNAs were isolated: clone CD60A1 codes for the cation-dependent mannose 6-phosphate receptor, clone CC6 is a human homologue of the bovine 39-kDa nuclear-encoded NADH:ubiquinone oxidoreductase subunit, and CD18 belongs to the family of tumor necrosis factor receptor proteins [20].
• However, neutrophils stimulated with PAF (20-200 nM) showed a dose-dependent increase in adherence that was largely (70%) mediated by the beta 2 (CD11/CD18) integrins; adherence was less dependent (50%) on fibroblast intercellular adhesion molecule-1 [21].

Physical interactions of LTBR

• TNFSF14/LIGHT is a member of the tumor necrosis factor superfamily that binds to lymphotoxin-beta receptor (LTbetaR) to induce cell death via caspase-dependent and caspase-independent pathways [22].
• Subsequently, a recombinant LT beta R was shown to bind LT alpha LT beta heteromeric complexes [1].
• The lymphotoxin-beta receptor (LT-betaR) has been shown to be the receptor for the membrane-bound lymphotoxin heterotrimers LTalpha1/beta2 and LTalpha2/beta1 [19].

Regulatory relationships of LTBR

• Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation [18].
• Changes in CD11/CD18 expression were blocked by the mitogen-activated protein kinase kinase inhibitor PD98059 [23].

Other interactions of LTBR

• The role of apoptosis signal-regulating kinase 1 in lymphotoxin-beta receptor-mediated cell death [24].
• The ability to augment TRAIL-initiated cell death was not observed with soluble lymphotoxin beta receptor or soluble death receptor 3, indicating that binding to LIGHT or TL1A alone is insufficient to trigger TRAIL sensitivity [25].
• Here, regulation of interferon-beta by LT beta R and TNFR signaling may play a crucial role in certain viral infections [26].
• Regulation of autoimmune regulator in the thymus via LT beta R implicates LT/LIGHT involvement in central tolerance [26].
• A positive correlation occurred between the IL-8 concentration and CD18 or CD1 1b densities on neutrophils in the synovial fluid (r = 0.75, P < 0.005 and r = 0.60, P < 0.05, respectively) [27].

Analytical, diagnostic and therapeutic context of LTBR

• Lymphocyte function-associated antigen-1beta (LFA-1beta) (CD18) expression was determined with flow cytometry, and myeloperoxidase secretion was analyzed with ELISA [28].
• Ligation of the lymphotoxin-beta receptor (LTbetaR) recruits tumor necrosis factor receptor-associated factor-3 (TRAF3) and initiates cell death in HT29 adenocarcinoma cells [29].
• After 4 d of NO inhalation (18 ppm), PMN form bronchoalveolar lavage (BAL) showed a reduction in both spontaneous H2O2 production (p<0.05) and beta 2 integrin CD11b/CD18 expression (p<0.05) [30].
• In the control group, neither tumor necrosis factor-alpha nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass [31].
• Only intravenous injection of wild-type PMNs could re-establish the Arthus reaction in CD18-/- mice [32].

References