Autocrine Regulation by IL-21 in the Generation

¶ … autocrine regulation by IL-21 in the generation of inflammatory T cells" from Nature 2007

Biological background and research findings/data

This article touches upon several important and popular areas of research interest in immunology and microbiology over the past two decades. The study of CDK4+ T cells has clearly been a well-financed and prioritized research subject since the role of this type of cell was identified as essential in the pathophysiology of HIV / AIDS. IL-21 in particular was identified as a regulator in NK cell activity and terminal differentiation shortly before the start of the last century (Biron 1999). IL-21 is a cytokine, measuring 15 kDa and consisting of four alpha helixes. Prior to this paper, published as a letter in Nature in 2007, there had been three major functions of IL-21, which is secreted from activated CD4+ T cells, in immunological pathways (Neely 1997).

IL-21 was first studied as a regulator in adaptive immune response, when natural killer (NK) cells have been activated by one of many known cytokines, including IL-15, to which IL-21 is genomically similar. IL-21 has been thought to interact with NK cells in the upregulation of CD16, an IgG receptor which mediates cytotoxicity triggered by antibody binding (Miller 2002). It has also been studied in the macrophage apoptotic IFN-gamma pathway. A third domain of IL-21 study has been in relation to its role in inducing apoptosis in terminally-differentiated NK cells, a stage of cell death signaling the transition from the innate immunological response to the adaptive immune response (Medzhitov 1997).

This article looked at an autocrine regulation role that IL-21 was found to have in the generation of inflammatory T cells. It was shown that the pathway of IL-21 in this pathway is STAT3 interacting with IL-6, which then induces IL-21 in T cells. It was demonstrated to be necessary for TH17 generation when STAT3 upregulated ROR-c. The autocrine function in which IL-21 has been found to operate was compared with the role of IFN-c in TH1 generation in IL-4 in TH2 generation. The authors concluded then that T cell differentiation is mediated by constituent parts of the innate immune response in a T-cell intrinsic manner via autocrine pathways, and that this represents a novel understanding of the interplay of the various immune responses than has been previously understood.

Reaction to Article

While the implications of the researchers' finding are very promising, there are some problems in the area of data presentation and clarity. It is a cause for concern when so few of the data plots and charts have error bars indicating the reliability of the experimental results and the likelihood of reproducing the same results if the experimental design were replicated. None of the experimental designs seemed flawed in and of themselves, but it would have been useful for the validity of the data to include a larger number of mouse specimens in the experiment.

With regard to the finding, there is no reason to doubt the ability of cytokines in the innate immune response to function in the T cell differentiation process at the outset of the adaptive immune response. This makes particular sense given the studies conducted examining the role of IL-21 in programmed apoptosis in NK cells at the end of the innate immune response.

Relevance of the article topic in relationship to society and immunology

The article is of particular importance as specific targets in treating inflammatory diseases are needed to enable more specialized and effective anti-inflammatory treatments. The mechanism by which IL-21 deficient mice were protected from the development of EAE is still not entirely understood and is an area of future research which may provide additional insight into the role of autocrine cytokines in the mediation of excessive inflammatory response.