Tuesday, 17 September 2013

Interleukin-27 inhibits T cell function

Chong WP, Horai R, Mattapallil MJ, Silver PB, Chen J, Zhou R, Sergeev Y, Villasmil R, Chan CC, Caspi RR. IL-27p28 inhibits central nervous system autoimmunity by concurrently antagonizing Th1 and Th17 responses. J Autoimmun. 2013 Sep doi:pii: S0896-8411(13)00109-1. 10.1016/j.jaut.2013.08.003. [Epub ahead of print]

Central nervous system (CNS) autoimmunity such as multiple sclerosis is accompanied by Th1 and Th17 responses. In experimental autoimmune encephalomyelitis (EAE), both responses are induced and can drive disease independently. Because immune responses have inherent plasticity, therapeutic targeting of only one pathway could promote the other, without reducing pathology. IL-27p28 antagonizes gp130, required for signaling by IL-27 and IL-6, which respectively promote Th1 and Th17 responses. We therefore examined its ability to protect the CNS by concurrently targeting both effector responses. Overexpression of IL-27p28 in vivo ameliorated EAE pathology and reduced tissue infiltration by Th1 and Th17 cells. Mechanistic studies revealed inhibition of Th1 and Th17 commitment in vitro and decreased lineage stability of pre-formed effectors in vivo, with reduction in expression of gp130-dependent transcription factors and cytokines. Importantly, IL-27p28 inhibited polarization of human T cells to the Th1 and Th17 effector pathways. The ability of IL-27p28 to inhibit generation as well as function of pathogenic Th1 and Th17 effector cells has therapeutic implications for controlling immunologically complex autoimmune diseases

Interleukin-27 (IL-27) is a heterodimeric cytokine belonging to the IL-12 family that is composed of two subunits; Epstein-Barr virus (EBV)-induced gene 3 (EBI3) (also known as IL-27B) and IL27-p28 (known as IL-30). IL-27 is produced by antigen-presenting cellsIL-27 plays an important function in regulating the activity of B- and T-lymphocytes. The effects of IL-27 are eliciting by its interaction with a specific cell-surface receptor complex composed of two proteins known as IL27R and gp130.

Glycoprotein 130 (also known as gp130, IL6-beta or CD130) forms one subunit of type I cytokine receptors within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction following cytokine engagement. 

Inhibiting IL-27 maybe yet another method for modulation of T cell function is this how beta interferon works as suggested by some?

No comments:

Post a Comment

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.