Sunday, October 9, 2011

Th17: thymus keeps it natural

IL-17-producing T cells, called T helper 17 cells (Th17) have been one of the main focus of immunological research since their discovery in 2006. Th17 cells gained such popularity for wrong reason: their involvement in bodies own tissue destruction or commonly known as autoimmune diseases. Very little is known about Th17 role in protection against infection (so far, we know that they contribute primarily in defense against fungi and extracellular bacteria). One peculiar feature of Th17 cells was the discovery that TGF-beta (in combination with IL-6 or IL-21) was needed for their generation, in in vitro assays, at least. This was interesting because TGF-beta is needed for the generation of Foxp3+ regulatory T cells (Tregs). According to current interpretation, the balance between Th17 and Tregs determines autoimmunity versus tolerance outcome.

If you are interesting to know more about Th17 cells, I will recommend reading the following paper recently published in Journal of Experimental Medicine. In this study (1), Kim et al, made several noteworthy observations: first, they showed that thymus from naive mice contains population of CD4 T cells expressing IL-17. Second, this thymic-derived Th17 cells are enriched in one particular T cell receptor gene, called V beta 3. Third, this Th17 cells need to interact with MHC class II molecules expressed on radioresistant thymic medullary epithelial cells to develop. Fourth, reduced T cell receptor signaling (Y145F mutation) favor their development. Fifth, the same Y145F mutation, however, prevented proper development/differentiation of peripheral, gut-associated Th17 cells.

It seems that paper represents the mix of two independent projects. However, the authors conclusions (and title of the paper) are mainly focused on results from only one project, namely, that (based on Y145F mutation) there are two, non-overlapping Th17 populations, one thymic-derived, called natural Th17 and another peripherally-converted.

David Usharauli

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