Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2.

Tumor-induced myeloid-derived suppressor cells (MDSC) contribute to immune suppression in tumor-bearing individuals and are a major obstacle to effective immunotherapy. Reactive oxygen species (ROS) are one of the mechanisms used by MDSC to suppress T cell activation. Although ROS are toxic to most cells, MDSC survive despite their elevated content and release of ROS.

Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells.

Effective cell-mediated antitumor immunity requires the activation of tumor-reactive T cells and the trafficking of activated T cells to tumor sites. These processes involve the extravasation of lymphocytes from the blood and lymphatics, and their homing to lymph nodes and tumors. L-selectin (CD62L) is an important molecule in these processes.

Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4.

Myeloid-derived suppressor cells (MDSC) are potent inhibitors of anti-tumor immunity that facilitate tumor progression by blocking the activation of CD4(+) and CD8(+) T cells and by promoting a type 2 immune response through their production of IL-10 and down-regulation of macrophage production of IL-12. MDSC accumulate in many cancer patients and are a significant impediment to active cancer immunotherapies. Chronic inflammation has been shown recently to enhance the accumulation of MDSC and to increase their suppression of T cells.

Interleukin-4 (IL-4) pathway.

Interleukin-4 (IL-4) is a cytokine produced by T(H)2 type helper T cells and by mast cells, basophils, and eosinophils. This cytokine can elicit many responses, some of which are associated with allergy and asthma. Studies with long-term cell lines and primary cells have revealed differences in the signaling between these two experimental systems.

Interleukin-13 (IL-13) pathway.

Interleukin-13 (IL-13), like IL-4, is a cytokine produced by T(H)2 type helper T cells in response to signaling through the T cell antigen receptor and by mast cells and basophils upon cross-linkage of the high-affinity receptor for immunoglobulin E (IgE). It is also produced by activated eosinophils. IL-13 induces many of the same responses as IL-4 and shares a receptor subunit with IL-4.

Interleukin-4 and interleukin-13 signaling connections maps.

Cytokines are inflammatory mediators important in responding to pathogens and other foreign challenges. Interleukin-4 (IL-4) and IL-13 are two cytokines produced by T helper type 2 cells, mast cells, and basophils. In addition to their physiological roles, these cytokines are also implicated in pathological conditions such as asthma and allergy.

Regulation of the dephosphorylation of Stat6. Participation of Tyr-713 in the interleukin-4 receptor alpha, the tyrosine phosphatase SHP-1, and the proteasome.

Signal transducer and activator of transcription 6 (Stat6) plays an important role in interleukin (IL)-4-induced responses. To analyze the regulation of Stat6 phosphorylation, cells were cultured in the continuous presence of IL-4 or after a pulse and washout. In the continual presence of IL-4, Stat6 remained phosphorylated for an extended period.