Nuestra compañera de laboratorio Ivana Nikolić, ha sido galardonada con dos proyectos de la Sociedad Europea de la Diabetes (EFSD) para estudiar el papel de las células T en el desarrollo de las enfermedades asociadas a la obesidad: el “EFSD/Lilly Young Investigator Award” y el “EFSD Rising Star Fellowship”. El Programa EFSD/Lilly Young Investigator Research Award Programme consta de una beca de 50.000 euros, mientras que en el caso del EFSD Rising Star Fellowship Programme, la financiación será de 30.000 euros.
La Dra. Nikolić recibió el Premio EFSD / Lilly Young Investigator y la Beca EFSD Rising Star durante el “EFSD Rising Star Symposium” patrocinado por Novo Nordisk en el prestigioso congreso de la Asociación Europea de la Diabetes que se celebra en Barcelona.
CD69 regulates lymphocyte egress from the thymus and lymph nodes through cis-interactions and the downregulation of surface sphingosine-1-phosphate (S1P) receptor-1 (S1P1). However, its role in the regulation of cell egress from bone marrow has not been extensively studied.
mTOR pathway activation in bone marrow (Image: Magdalena Leiva).
We show here that CD69 targeting induced rapid and massive mobilization of BM leukocytes, which was inhibited by desensitization to S1P with FTY720. This mobilization was reproduced with anti-human CD69 mAb treatment of mice expressing human CD69. In this strain, the mobilization occurred to the same extent as that induced by AMD3100. The anti-human CD69 treatment highly increased LSK and CLP cell proliferation and numbers, both in the periphery and in the BM, and also augmented S1P1 and CXCR4 expression. Additionally, increased mTOR, p70S6K, S6, and 4E-BP1 phosphorylation was detected after in vivo anti-CD69 treatment in the bone marrow. Importantly, mTOR inhibition with rapamycin inhibited anti-huCD69-induced mobilization of hematopoietic stem and progenitor cells (HSPCs).
Together, our results indicated that CD69 targeting induces not only mobilization but also high proliferation of HSPCs, and thus is crucial for precursor cell replenishment over time. These results suggest that anti-CD69 mAbs are putative novel candidates for mobilization strategies.