TY - JOUR AU - Marianna Di Scala, AU - Irene Gil-Fariña, AU - Lucia Vanrell, AU - Rodrigo Sánchez-Bayona, AU - Diego Alignani, AU - Cristina Olagüe, AU - Africa Vales, AU - Pedro Berraondo, AU - Jesús Prieto, AU - Gloria González-Aseguinolaza, PY - 2015/08/03 Y2 - 2024/03/29 TI - Chronic exposure to IFNα drives medullar lymphopoiesis towards T-cell differentiation in mice JF - Haematologica JA - haematol VL - 100 IS - 8 SE - Articles DO - 10.3324/haematol.2014.115410 UR - https://haematologica.org/article/view/7457 SP - 1014-1022 AB - Interferon-α is a potent antiviral agent and a vigorous adjuvant in the induction of T-cell responses but its use is limited by hematologic toxicity. Interferon-α alters hematopoietic stem cell dormancy and impairs myelocytic and erythrocytic/megakaryocytic differentiation from hematopoietic progenitors. However, the effect of chronic interferon-α exposure on hematopoietic precursors has still not been well characterized. Here, we transduced the liver of mice with an adenoassociated vector encoding interferon-α to achieve sustained high serum levels of the cytokine. The bone marrow of these animals showed diminished long-term and short-term hematopoietic stem cells, reduction of multipotent progenitor cells, and marked decrease of B cells, but significant increase in the proportion of CD8+ and CD4+CD8+ T cells. Upon adoptive transfer to RAG−/− mice, bone marrow cells from interferon-α-treated animals generated CD4+ and CD8+ T cells while CD19+, CD11b+ and NK1.1+ lineages failed to develop. These effects are associated with the transcriptional downregulation of transcription factors involved in B-cell differentiation and modulation of key factors for T-cell development. Thus, sustained interferon-α exposure causes hematopoietic stem cells exhaustion and drives common lymphoid progenitors towards T-cell generation. ER -