Suppressor of Cytokine Signaling 2 Negatively Regulates NK Cell Differentiation by Inhibiting JAK2 Activity

• Published in: Scientific reports 2017-04, Vol.7 (1), p.46153-46153, Article 46153
• Main Authors: Kim, Won Sam, Kim, Mi Jeong, Kim, Dong Oh, Byun, Jae-Eun, Huy, Hangsak, Song, Hae Young, Park, Young-Jun, Kim, Tae-Don, Yoon, Suk Ran, Choi, Eun-Ji, Jung, Haiyoung, Choi, Inpyo
• Format: Article
• Language: English
• Subjects: 13/44; 13/95; 14; 14/19; 38/1; 38/109; 38/22; 38/70; 38/90; 42/89; 45/29; 45/77; 59; 631/250/232/2058; 631/250/2504/2506; 64/60; 96/34; Adaptive immunity; Bone marrow; Cell differentiation; Cytokines; Genes; Humanities and Social Sciences; Janus kinase; Janus kinase 2; Kinases; Lungs; Melanoma; Metastases; multidisciplinary; Natural killer cells; Rodents; Science; Spleen; Stat5 protein; Stem cell transplantation; Stem cells; Transplantation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep46153

Suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine responses. Although recent reports have shown regulatory roles for SOCS proteins in innate and adaptive immunity, their roles in natural killer (NK) cell development are largely unknown. Here, we show that SOCS2 is involved in NK cell development. SOCS2 −/− mice showed a high frequency of NK cells in the bone marrow and spleen. Knockdown of SOCS2 was associated with enhanced differentiation of NK cells in vitro , and the transplantation of hematopoietic stem cells (HSCs) into congenic mice resulted in enhanced differentiation in SOCS2 −/− HSCs. We found that SOCS2 could inhibit Janus kinase 2 (JAK2) activity and JAK2-STAT5 signaling pathways via direct interaction with JAK2. Furthermore, SOCS2 −/− mice showed a reduction in lung metastases and an increase in survival following melanoma challenge. Overall, our findings suggest that SOCS2 negatively regulates the development of NK cells by inhibiting JAK2 activity via direct interaction.