Interferon-γ Promotes Inflammation and Development of T-Cell Lymphoma in HTLV-1 bZIP Factor Transgenic Mice
HTLV-1 is a retrovirus which causes a cancer, ATL, and inflammatory diseases of several tissues, such as the spinal cord, eye, skin, and lung. Although these HTLV-1-mediated malignant and inflammatory diseases are recognized as distinct pathological entities, an increased number of HTLV-1 infected cells and enhanced migration/infiltration of infected cells into the lesions are common features of these diseases. Indeed, several clinical observations have suggested a causal link between inflammation and ATL (see Discussion). In order to investigate this issue, appropriate animal models are indispensable. Among HTLV-1-encoded regulatory/accessory proteins, HTLV-1 bZIP factor (HBZ) is thought to be critical to HTLV-1-mediated pathogenesis. We previously reported that HBZ transgenic (HBZ-Tg) mice which express HBZ in CD4+ T cells developed both systemic inflammation and T-lymphomas, indicating that they are suitable to evaluate the link, if any, between these phenomena. In this study, we generated several new genetically engineered strains by modifying HBZ-Tg mice, and found that IFN-γ is an accelerator of HBZ-induced inflammation. Importantly, we show that the incidence of inflammation is correlated with that of lymphomagenesis in HBZ-Tg. These findings indicate that modification of T-cell machinery by HBZ is closely associated with both HTLV-1-associated inflammatory diseases and ATL.
Vyšlo v časopise:
Interferon-γ Promotes Inflammation and Development of T-Cell Lymphoma in HTLV-1 bZIP Factor Transgenic Mice. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005120
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1005120
Souhrn
HTLV-1 is a retrovirus which causes a cancer, ATL, and inflammatory diseases of several tissues, such as the spinal cord, eye, skin, and lung. Although these HTLV-1-mediated malignant and inflammatory diseases are recognized as distinct pathological entities, an increased number of HTLV-1 infected cells and enhanced migration/infiltration of infected cells into the lesions are common features of these diseases. Indeed, several clinical observations have suggested a causal link between inflammation and ATL (see Discussion). In order to investigate this issue, appropriate animal models are indispensable. Among HTLV-1-encoded regulatory/accessory proteins, HTLV-1 bZIP factor (HBZ) is thought to be critical to HTLV-1-mediated pathogenesis. We previously reported that HBZ transgenic (HBZ-Tg) mice which express HBZ in CD4+ T cells developed both systemic inflammation and T-lymphomas, indicating that they are suitable to evaluate the link, if any, between these phenomena. In this study, we generated several new genetically engineered strains by modifying HBZ-Tg mice, and found that IFN-γ is an accelerator of HBZ-induced inflammation. Importantly, we show that the incidence of inflammation is correlated with that of lymphomagenesis in HBZ-Tg. These findings indicate that modification of T-cell machinery by HBZ is closely associated with both HTLV-1-associated inflammatory diseases and ATL.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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