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TLR2 Ligation Modulates the Balance between Regulatory and Th17 Function in Human T-Cells: Implications for Multiple Sclerosis

Abhishek Kumar , Abhishek Kumar , Mukanthu Nyirenda , Bruno Gran

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New Indian Journal of Surgery 3(3):p 209-209, July - September 2012. | DOI:

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Abstract

  By maintaining immunological self-tolerance, a subset of lymphocytes known as regulatory T cells (Tregs) play a key role in preventing the development of autoimmunity. These Tregs express a host of receptors,
including pathogen recognition receptors (PRRs) of the innate immune system known as Toll-like receptors (TLRs). Ligation of these TLRs with pathogenic antigens known as pathogen associated molecular patterns (PAMPs) has been reported to modulate Treg function. Ligation of TLR2 in particular, has been reported to reduce the suppressive capacity of murine and human Tregs by unknown mechanisms. However this was recently elucidated upon when ligation of the TLR1/2 heterodimer was observed to enhance interleukin (IL)-6 and transforming growth factor (TGF)-â expression by Tregs. These cytokines have a vital role in regulating the reciprocal and mutually inhibitory relationship between Tregs and T-helper (Th) 17 cells- a subset of lymphocytes which are key in the pathogenesis of autoimmune diseases and protection against bacterial infections. The presence of IL-6 can alter the balance between Tregs and Th17 cells in favour of the latter by inducing differentiation of naïve T cells towards the Th17 lineage, whilst also inducing concomitant inhibition of Treg differentiation.

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