Introduction: STKE Focus Issue on Signaling in the Immune System

Abstract

In conjunction with this week's special issue of Science on Vaccines and Immunity ( ), the STKE presents a focus issue on Signaling in the Immune System. How infections are most effectively cleared often depends on the type of T helper (TH) cell response elicited. TH1 cell responses are effective in clearing infections caused by intracellular bacteria, but TH2 cell responses are critical for fighting extracellular parasitic pathogens. Interestingly, certain infectious pathogens can increase the likelihood of successful infection through subversion of the immune response. They elicit the incorrect type of TH response; thus, their rate of clearance is impaired and the probability of successful infection increases. Cytokines and transcription factors are important for TH cell differentiation, but it is not clear whether they act in instruction (the order to differentiate into TH1 or into TH2), (proliferation signals for survival and population expansion), or both. The Perspective by Nelson ( ) discusses a recent paper that demonstrates that the cytokine interleukin-12 is essential for the selection phase of TH cell maturation, whereas the transcription factor T-bet is necessary for instruction. Koretzky and Singer ([http://stke.sciencemag.org/cgi/cm/CMP_7019][1]) have created a Connections Map that details the signaling pathways leading from the T cell antigen receptor (TCR) to specific genes that are expressed in response to TCR activation. The authors also provide a figure detailing the protein-protein interactions that occur following TCR activation. This figure can be viewed by clicking on a link from the abstract that accompanies the canonical pathway TCR in the Connections Map. This is the STKE's first immune cell receptor Connections Map, which will be followed by the B cell antigen receptor pathway. Organisms fend off pathogens by recruiting leukocytes to sites of infection. Leukocytes are recruited through chemotaxis, whereby the cells migrate toward an increasing gradient of chemoattractive substances. Once an infection is cleared, an organism no longer needs to have recruited leukocytes at the site of infection; therefore, the immune system requires a way to switch off the chemotactic response. Fernandis and Ganju ( ) discuss recent findings that Slit, a protein known to repulse the migration of neurons, has a similar role in immunity. Slit functions to inhibit the chemotactic responses of leukocytes though a process that involves Slit's receptor Robo and CXCR4, the receptor for the chemoattractant protein stromal cell-derived factor-1 (SDF-1). Because CXCR4 is an important coreceptor for human immunodeficiency virus (HIV) infection of immune cells, there may be a role for Slit, or a rationally designed agent based on Slit, as a therapeutic factor in preventing HIV infection. Featured in this Focus Issue on Signaling in the Immune System Related Resources at STKE [1]: pending:yes