Lack of Both Nucleotide-Binding Oligomerization Domain-Containing Proteins 1 and 2 Primes T Cells for Activation-Induced Cell Death
| Autor: | Sashi G. Kasimsetty, Alana A. Shigeoka, Andrew T. Scheinok, Dianne B. McKay, Amanda L. Gavin, Richard J. Ulevitch |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Isoantigens T cell T-Lymphocytes Immunology Nod2 Signaling Adaptor Protein Down-Regulation Graft vs Host Disease Biology Adaptive Immunity Lymphocyte Activation Article 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine Immune system Nod1 Signaling Adaptor Protein medicine Immunology and Allergy Cytotoxic T cell Animals Antigen-presenting cell Innate immune system Cell Death Pattern recognition receptor Proto-Oncogene Proteins c-mdm2 Acquired immune system Genes p53 Immunity Innate Cell biology body regions Disease Models Animal 030104 developmental biology medicine.anatomical_structure Receptors Pattern Recognition 030215 immunology Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 199(3) |
| ISSN: | 1550-6606 |
| Popis: | Nucleotide-binding oligomerization domain (Nod)–containing proteins Nod1 and Nod2 play important roles in the innate immune response to pathogenic microbes, but mounting data suggest these pattern recognition receptors might also play key roles in adaptive immune responses. Targeting Nod1 and Nod2 signaling pathways in T cells is likely to provide a new strategy to modify inflammation in a variety of disease states, particularly those that depend on Ag-induced T cell activation. To better understand how Nod1 and Nod2 proteins contribute to adaptive immunity, this study investigated their role in alloantigen-induced T cell activation and asked whether their absence might impact in vivo alloresponses using a severe acute graft versus host disease model. The study provided several important observations. We found that the simultaneous absence of Nod1 and Nod2 primed T cells for activation-induced cell death. T cells from Nod1 × 2−/− mice rapidly underwent cell death upon exposure to alloantigen. The Nod1 × 2−/− T cells had sustained p53 expression that was associated with downregulation of its negative regulator MDM2. In vivo, mice transplanted with an inoculum containing Nod1 × 2−/− T cells were protected from severe graft versus host disease. The results show that the simultaneous absence of Nod1 and Nod2 is associated with accelerated T cell death upon alloantigen encounter, suggesting these proteins might provide new targets to ameliorate T cell responses in a variety of inflammatory states, including those associated with bone marrow or solid organ transplantation. |
| Databáze: | OpenAIRE |
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