Osteopontin: a new addition to the constellation of cytokines which drive T helper cell type 1 responses in Crohn’s disease: Figure 1

Osteopontin, a cytokine which promotes Th1 immune responses, is overexpressed in the gut of patients with Crohn’s disease or ulcerative colitis. The main cellular source of this cytokine appears to be gut plasma cells. Crohn’s disease appears to be caused by an excessive CD4+ T helper cell type I response directed against undefined antigens of the commensal bacterial flora.1 T cells from affected areas of Crohn’s disease mucosa produce enhanced amounts of interferon γ (IFN-γ) and tumour necrosis factor α. Other markers of Th1 cells, such as expression of the transcription factor T-bet, the high affinity β2 chain of the interleukin 12 (IL-12) receptor, and activated STAT4, all indicate that the mucosal environment in Crohn’s disease favours Th1 polarisation.1 It is important to emphasise that CD4 T cells in normal bowel are also Th1 skewed and express T-bet, so that the differences seen in Crohn’s disease are quantitative rather than qualitative.2 Normal mucosal T cells are however susceptible to apoptosis, whereas this is not the case in Crohn’s disease,3 suggesting that it is the persistence and accumulation of Th1 cells which drives tissue injury. Factors which commit virgin T cells to the Th1 or Th2 pathway are still under investigation. T-bet appears to be of primary importance.4 It is induced by IFN-γ itself and is capable of promoting IFN-γ production, not only in Th1 cells, but also in Th2 cells. T-bet also increases expression of the IL-12Rβ2 chain. Macrophage and dendritic cell derived IL-12 is crucial in Th1 immune responses.5 The …