Academic Journal
Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress
العنوان: | Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress |
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المؤلفون: | Michiko Ichii, Kenji Oritani, Jun Toda, Hideaki Saito, Henyun Shi, Hirohiko Shibayama, Daisuke Motooka, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Kodai Saitoh, Daisuke Okuzaki, Tadashi Matsuda, Yuzuru Kanakura |
المصدر: | Haematologica, Vol 106, Iss 2 (2020) |
بيانات النشر: | Ferrata Storti Foundation, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Diseases of the blood and blood-forming organs |
مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
الوصف: | Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IκB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 0390-6078 1592-8721 |
Relation: | https://haematologica.org/article/view/9620; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
DOI: | 10.3324/haematol.2019.225573 |
URL الوصول: | https://doaj.org/article/138b5f117e5347b9aa4e85806685e47d |
رقم الانضمام: | edsdoj.138b5f117e5347b9aa4e85806685e47d |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 03906078 15928721 |
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DOI: | 10.3324/haematol.2019.225573 |