IL-15 can signal via IL-15Rα, JNK, and NF-κB to drive RANTES production by myeloid cells.

نویسندگان

  • Meghan J Chenoweth
  • M Firoz Mian
  • Nicole G Barra
  • Tommy Alain
  • Nahum Sonenberg
  • Jonathan Bramson
  • Brian D Lichty
  • Carl D Richards
  • Averil Ma
  • Ali A Ashkar
چکیده

IL-15 plays many important roles within the immune system. IL-15 signals in lymphocytes via trans presentation, where accessory cells such as macrophages and dendritic cells present IL-15 bound to IL-15Rα in trans to NK cells and CD8(+) memory T cells expressing IL-15/IL-2Rβ and common γ chain (γ(c)). Previously, we showed that the prophylactic delivery of IL-15 to Rag2(-/-)γ(c)(-/-) mice (mature T, B, and NK cell negative) afforded protection against a lethal HSV-2 challenge and metastasis of B16/F10 melanoma cells. In this study, we demonstrated that in vivo delivery of an adenoviral construct optimized for the secretion of human IL-15 to Rag2(-/-)γ(c)(-/-) mice resulted in significant increases in spleen size and cell number, leading us to hypothesize that IL-15 signals differently in myeloid immune cells compared with lymphocytes, for which IL-15/IL-2Rβ and γ(c) expression are essential. Furthermore, treatment with IL-15 induced RANTES production by Rag2(-/-)γ(c)(-/-) bone marrow cells, but the presence of γ(c) did not increase bone marrow cell sensitivity to IL-15. This IL-15-mediated RANTES production by Rag2(-/-)γ(c)(-/-) bone marrow cells occurred independently of the IL-15/IL-2Rβ and Jak/STAT pathways and instead required IL-15Rα signaling as well as activation of JNK and NF-κB. Importantly, we also showed that the trans presentation of IL-15 by IL-15Rα boosts IL-15-mediated IFN-γ production by NK cells but reduces IL-15-mediated RANTES production by Rag2(-/-)γ(c)(-/-) myeloid bone marrow cells. Our data clearly show that IL-15 signaling in NK cells is different from that of myeloid immune cells. Additional insights into IL-15 biology may lead to novel therapies aimed at bolstering targeted immune responses against cancer and infectious disease.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

IL-15 Can Signal via IL-15Ra, JNK, and NF-kB To Drive RANTES Production by Myeloid Cells

متن کامل

Salidroside regulates the expressions of IL-6 and defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways

Objective(s): To reveal the detailed mechanism underlying the functions of salidroside on the inflammation of intestinal epithelial cells during IBD.Materials and Methods: Quantitative real-time PCR was employed to assess the expression of IL-6, IL-10, and α-defensins 5 and 6. ELISA assay was performed to measure the secretion of IL-6 and IL-10. MTT assay was used to determine the cell viabilit...

متن کامل

Reactive oxygen species mediate TNF-α-induced inflammatory response in bone marrow mesenchymal cells

Objective(s): It is generally believed that the inflammatory response in bone marrow mesenchymal stem cells (BMSCs) transplantation leads to poor survival and unsatisfactory effects, and is mainly mediated by cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α). In this study, we explored the mechanisms underlying the TNF-α-induced inflammatory ...

متن کامل

The effect of down-regulation of CCL5 on lipopolysaccharide-induced WI-38 fibroblast injury: a potential role for infantile pneumonia

Objective(s): Aberrant expression of CCL5 has been found in several kinds of inflammatory diseases, and the roles of CCL5 in these diseases have also been reported. However, the role of CCL5 in infantile pneumonia is still unclear. Thus, the function and acting mechanism of CCL5 in the in vitro model of infantile pneumonia were researched in this study. Materials and Methods: Human fetal lung f...

متن کامل

Gambogic acid inhibits LPS-induced macrophage pro-inflammatory cytokine production mainly through suppression of the p38 pathway

Objective(s): In traditional Chinese medicine, gamboge can detoxify bodies, kill parasites, and act as a hemostatic agent. Recent studies have demonstrated that gambogic acid (GBA) suppressed inflammation in arthritis, and also presented antitumor effect. Thus, this study investigated the new biological properties of GBA on macrophages.Materials and Methods: RAW 264.7 cells were pretreated with...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of immunology

دوره 188 9  شماره 

صفحات  -

تاریخ انتشار 2012