From a gene-centric to whole-proteome view of differentiation of T helper cell subsets

Abstract

Proper differentiation of naïve T helper cells into functionally distinct subsets is of critical importance to human health. Consequently, the process is tightly controlled by a complex intracellular signalling network. To dissect the regulatory principles of this network, immunologists have early on embraced system-wide transcriptomics tools, leading to identification of large panels of potential regulatory factors. In contrast, the use of proteomics approaches in T helper cell research has been notably rare, and to this date relatively few high-throughput datasets have been reported. Here, we discuss the importance of such research and envision the possibilities afforded by mass spectrometry-based proteomics in the near future.

Keywords: T cell activation; T helper cell; mass spectrometry; proteomics; systems biology; transcriptomics.

Figure 1:

A simplistic model of the subset differentiation of T helper cells. The differentiation is initiated by contact with cognate antigen peptide–MHC complex on the antigen presenting cell. The direction of differentiation is largely determined by cytokines, the effects of which are relayed by specific STAT proteins. The STATs, together with downstream lineage-specifying transcription factors, orchestrate subset-specific gene expression programs, including production of hallmark cytokines.

Figure 2:

Proteomics approaches to elucidate processes leading to the development of T helper effector subsets. Th0, Th1 and Th2 refer to experimental conditions where cells were activated (Th0) and cultured in presence or absence of cytokines promoting differentiation of Th1 or Th2 cells.