Research Description

SOCS-1 and Regulatory T-cell Development

The specific project has aims to investigate the role of SOCS-1 in regulatory T-cell development. To give some background, cytokines are highly involved in the development, differentiation, and maturation processes for lymphoid cells. The cytokines activate the JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway. In regulation of this, the suppressor of cytokine signaling (SOCS) proteins function to inhibit these cytokine signaling pathways and in fact work in much of a negative feedback type mechanism. However, with more studies using gene-targeted and knockout mice (mice that do not express or have a certain gene or gene product) important roles of SOCS proteins are being discovered.

SOCS-1 deficiency leads to increased hypersensitivity to lipopolysaccharide (LPS). As a result, macrophages and dendritic cells in SOCS-1 deficient mice produce elevated levels of pro-inflammatory cytokines, specifically tumour-necrosis factor (TNF), Interleukin-12 (IL-12), and Interferon-gamma (INF-γ) from T cells and natural killer cells in response to LPS. The spleens of SOCS-1 deficient mice have higher numbers of CD8α+ dendritic cells and strongly favor the development of CD8+ single positive (SP) thymocyte cells. The SOCS-1 deficient MHC-class II restricted transgenic T cells actually differentiate into CD8+SP cells, rather than CD4+ T cells, which they are normally destined to become. Therefore it is likely that SOCS-1 plays a role in the maturation of T cells although the role of SOCS-1 in the development of regulatory T cells has not been characterized. This research has high implications towards a better understanding of the and perhaps even steps to wards the improvement of immune responses. It is evident that naturally occurring CD25+CD4+ regulatory T cells are involved in the maintenance of immunological self-tolerance. For example, the regulatory T cells have been shown to prevent immunological self reactivity.