Disease relevance of Ltbr

• Signaling through the lymphotoxin beta receptor induces the death of some adenocarcinoma tumor lines [1].
• The lymphotoxin beta receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes [2].
• A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection [3].
• Suppression of established experimental autoimmune encephalomyelitis and formation of meningeal lymphoid follicles by lymphotoxin beta receptor-Ig fusion protein [4].
• These antibodies recognized a mouse LTbetaR-Ig fusion protein as well as endogenous LTbetaR on a variety of mouse fibroblast and fibrosarcoma cell lines [5].

Psychiatry related information on Ltbr

• In reactive disorders, a population of activated neutrophils with high CD45 and CD18 expression was detected [6].

High impact information on Ltbr

• The phenotypes of aly/aly mice are more severe than those of Ltbr-/- mice, however, indicating involvement of Nik in signal transduction mediated by other receptors [7].
• Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling [8].
• CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function [9].
• To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models [9].
• Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes [10].

Chemical compound and disease context of Ltbr

• We demonstrate that a T cell-restricted ligand, homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpesvirus entry mediator on T cells (LIGHT), signaling through the lymphotoxin receptor (LTbetaR) expressed on mature hepatocytes induces massive hepatomegaly [11].
• These results suggest the importance of beta2 integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease [12].
• LIGHT is a member of the tumor necrosis factor (TNF) superfamily, and its function is mediated by at least two receptors, including lymphotoxin beta receptor (LTbetaR) and herpes simplex virus entry mediator [13].
• However, when ICAM-1-, but not CD18-, deficient mice were pretreated with fucoidin, the adverse effects of PAF were markedly reduced; survival was 100%, although hypotension still developed [14].

Biological context of Ltbr

• The failure to properly express CII in mTECs of Lta(-/-) and Ltbr(-/-) mice leads to overt autoimmunity to CII and exquisite susceptibility to arthritis [15].
• The gene encoding mouse LT beta R, Ltbr, contains 10 exons spanning 6.9 kb and maps to mouse chromosome 6, which is closely linked to Tnfr1, consistent with the tight linkage of the human homologue of these genes on chromosome 12p13 [16].
• The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues [17].
• The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways [18].
• Therefore, LTbeta-R signaling during gestation is not sufficient to establish normal cellular microarchitecture [19].

Anatomical context of Ltbr

• Thus, LTbeta-R signaling mediates lymph node genesis [19].
• Thus, the LTbetaR proves pivotal for the ontogeny of the secondary lymphoid tissues [17].
• LTbetaR-/- mice lacked Peyer's patches, colon-associated lymphoid tissues, and all lymph nodes [17].
• To establish in which cell types expression of LTbetaR, LTbeta, and TNF is required for GC formation, LTbetaR-/-, LTbeta-/-, TNF-/-, B cell-deficient (BCR-/-), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice [20].
• Thus, development of splenic FDC networks depends on expression of LTbeta and TNF by B lymphocytes and LTbetaR by radioresistant stromal cells [20].

Associations of Ltbr with chemical compounds

• Since signaling through other members of this receptor family can induce cell death, e.g., the TNF and Fas receptors, it is important to determine if similar signaling events can be communicated via the LT-beta-R [1].
• Loss of LTbeta and LTbeta receptor signaling reduced the number of oval cells expressing A6 and muscle pyruvate kinase [21].
• Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L-arginine [22].
• To investigate LTbetaR-specific mast cell activation, the LTbetaR on BMMC from either wild-type or LTbetaR-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin [23].
• These results indicate that CD18 is critically involved in vivo in activating leukocytes to produce cytokines in response to LPS [24].

Physical interactions of Ltbr

• LIGHT, a newly identified TNF family member, is a costimulatory molecule for T cells and binds to LTbetaR and herpes virus entry mediator (HVEM) in vitro [25].

Regulatory relationships of Ltbr

• METHODS: Soluble LTbeta receptor (LTbetaR) immunoglobulin fusion protein was used to inhibit the LTalpha/beta/light axis in two independent rodent models of colitis: CD45RBhi CD4(+)-reconstituted SCID mice and bone marrow-transplanted tg26 mice (BM --> tg26) [26].
• Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1beta and TNF-alpha genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment [12].
• Normal differentiation of thymic MECs requires LTbetaR ligand on thymocytes and LTbetaR together with nuclear factor-kappaB-inducing kinase (Nik) in thymic epithelial cells [27].
• Leukocyte recruitment in CD18 null but not wild-type mice is significantly blocked by an mAb to E-selectin [28].
• Thus, LTbetaR pathway inhibition ameliorates DSS-induced experimental chronic colitis in mice by MAdCAM-1 down-regulation entailing reduced lymphocyte margination and extravasation into the inflamed mucosa [29].

Other interactions of Ltbr

• Lymph nodes developed in LTalpha-/- mice treated in utero with agonist anti-LTbeta-R monoclonal antibody [19].
• The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB [18].
• In conclusion, whereas normal splenic microarchitecture and isotype switch might require the LT beta receptor, differentiation of FDC network, development of germinal centers, and full IgG response depend on signaling via TNFR1 [30].
• Our data indicate an important role of p52-RelB heterodimers in lymphoid organ development downstream of LTbetaR, NIK and IKKalpha [31].
• These results indicate that LTbetaR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition [32].

Analytical, diagnostic and therapeutic context of Ltbr

• Lymphotoxin beta receptor (LTbetaR)-/- mice were created by gene targeting [17].
• Flow cytometry revealed that the LT beta R is expressed on pulmonary macrophages obtained after digestion of M. tuberculosis-infected lungs [2].
• To better understand the role of LT in development, the expression patterns of LTbeta and LTbetaR mRNA were examined by in situ hybridization in the developing mouse embryo [33].
• However, NIK was selectively required for gene transcription induced through ligation of LTbeta receptor but not TNF receptors [34].
• Furthermore, we find that about 5% of splenic DCs are undergoing cell division, and the number of dividing CD8- DCs is disproportionately reduced in the absence of the LT beta R. In parabiosis experiments, splenic DCs were only partially replaced by circulating precursors over a 6 week period [35].

References