Search results

Sort By:

Limit search:

Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance

100%

Matsumoto M.

Thymic epithelial cells (TECs) play pivotal roles in the establishment of self tolerance through critical dialogue with developing thymocytes. Unique actions of two transcriptional regulators within TECs, NF-kB-inducing kinase (NIK) and an autoimmune regulator (AIRE), for the establishment of self tolerance have recently been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice) and gene-targeted mice, respectively. Previous studies have demonstrated essential roles of NIK downstream of the lymphotoxin-beta receptor (LTbetaR), which is essential for the development of secondary lymphoid organs; aly mice lack all lymph nodes and Peyer's patches because of the defective LTbetaR signaling. Additional roles of NIK in thymic organogenesis downstream of LTbetaR, mainly through the developmental regulation of TECs, have now emerged, although the corresponding ligand(s) for LTbetaR participating in this action have not been fully characterized. In contrast, AIRE, a gene responsible for the development of an organ-specific autoimmune disease that demonstrates monogenic autosomal recessive inheritance, contributes to the establishment of self tolerance probably by controlling the expression of self antigens through yet undetermined molecular mechanisms. Thus it is highly likely that a group of genes control self-tolerance within TECs through unique and coordinated actions, and that an understanding of this process would help to unravel the pathogenesis of autoimmune disease.

Two receptor theory in innate activation: studies on the receptors for bacillus Culmet guillen-cell wall skeleton (BCG-CWS)

33%

Seya T., Matsumoto M., Tsuji S., Begum N. A., Nomura M., Azuma I., Hayashi A., Toyoshima K.

Archivum Immunologiae et Therapiae Experimentalis

2001

vol. 49

issue 1 suppl.

13-22

Activation of the innate immune system is a prerequisite for the maturation of dendritic cells (DC) and macrophages (M?) followed by clonal expansion of the lymphocytes, targeting cells expressing 'non-self' angitens. Microbes usually have a component competent to active DC/M? for antigens presentation. This component has been colled adjuvant, but recently renamed pathogen-associated molecular pattern (PAMP) or modulin based on its molecular identification. Here, we propose the hypothesis that DC/M? express two sorts of receptors for PAMP, whose signaling pathways lead to a sufficient antigen (Ag)-presenting state. In bacterial infection, a Toll-like receptor (TLR) and an uptake receptor participate in DC maturation and M? activation. Likewise, with a number of viruses, two of the receptors with short consensus repeats (SCR), immunoglobulin-like domains or chemokine receptor-like motifs etc. induce functional modulation of DC/M?. In immune therapy for cancer, primary activation of the innate system would be essential for tumor Ag-specific T cell augmentation. Cancer cells express tumor-associated Ag but barely co-express PAMP, which situation does not allow for the activation of innate immune responses. Supplementing tumor-associated Ag with PAMP may be an effective therapy for patients with cancer. Here, we discuss the possibility of an innate immune therapy for cancer with references to bacillus Culmet guillen cell-wall skeleton (GCG-CWS).

Refine search results

2 Archivum Immunologiae et Therapiae Experimentalis

1 2007

1 2001

2 Matsumoto M.

1 Azuma I.

1 Begum N. A.

1 Hayashi A.

1 Nomura M.

1 Seya T.

1 Toyoshima K.

1 Tsuji S.

Search results

Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance

Two receptor theory in innate activation: studies on the receptors for bacillus Culmet guillen-cell wall skeleton (BCG-CWS)