We would like to highlight a new community resource: the Immunological Proteome Resource (ImmPRes; http://immpres.co.uk/). ImmPRes aims to provide an in-depth high-quality map of the immune cell proteomes. It is an initiative inspired by resources such as ImmGen1, in which systematic analyses of RNA expression in immune cells have yielded invaluable biological insights about lymphocyte populations. ImmPRes maps the proteomes of immune cells rather than the transcriptome, which is important because changes in rates of protein synthesis and degradation mean that mRNA levels are not always effective predictors of cellular protein abundance2. There are thus clear examples of discordance between mRNA and protein abundance in T cells that reflect the ability of post-transcriptional mechanisms to control T cell proteomes3. Because proteins are the molecules that structure cells and control almost all metabolic processes and regulatory mechanisms4, there is enormous value in the characterization of cellular proteomes to understand lymphocyte identity. Fortunately, technological advances in high-resolution mass spectrometry have made it feasible to characterize cell proteomes quantitatively. The technology can be used to explore how immune cells remodel their proteomes when they respond to immune or environmental stimuli or when key signaling networks are disrupted. Proteomic data can provide extensive information about the cellular repertoires of proteins to create an objective understanding of cell ‘identity’. For example, knowledge of the abundance of metabolic enzymes, nutrient transporters, ribosomes, and translational enhancers and repressors enables the assessment of the metabolic capacity of different lymphocyte populations.
To leverage value from proteomic datasets, an easily interrogated online resource that enables rapid exploration of the protein landscape of key immune cells is vital. There is a resource focused on subsets of peripheral blood-derived human leukocytes5; however, no current mouse equivalent exists. We have therefore developed ImmPRes as a resource to integrate data derived from high-resolution mass spectrometry analysis of mouse hematopoietic populations. ImmPRes displays proteomic data of T cell subsets from lymph nodes, spleen, gut and liver, plus T cell populations activated in vitro with antigen and/or inflammatory cytokines. It includes datasets that map how the triggering of antigen receptors remodels the proteomes of naive CD4+ and CD8+ T cells. It enables a comparison of the proteomes of different in vitro-generated CD4+ T effector populations and shows how cytokines differentially affect the proteomes of cytotoxic T cells. The resource also shows how inhibition of key signaling pathways or the loss of important transcription factors or changes in environmental conditions shapes T cell proteomes. Furthermore, the major splenic and lymph node B cell populations are characterized, and the effect on B cell proteomes of B cell activation in vitro via antigen receptors, co-stimulators, cytokines and innate stimuli is examined. The resource also includes proteomes of innate immune cells with datasets from natural killer (NK) cells, neutrophils and bone marrow-derived mast cells and macrophages.
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