Interleukin-22's messy Nature

One way to determine if a research article published in prestigious journal comes with many “holes” is to look at its submission and acceptance time. If it is more than 6 months, it is highly likely an article is of low quality.

Here is one example of such article (1). It was published, after more than 1 year of review process, in most prestigious journal Nature and came from famous biotech company Genentech. 

You may wonder why Nature has published it? No idea.

This study focused on IL-22 and its role in metabolic syndrome, like obesity or defense against intestinal inflammation.

First, the authors showed that obese mice (ob/ob, db/db, or HDF) express less IL-22 compared to wild-type or lean mice.

Second, obese mice due to leptin signaling defect (ob/ob and db/db) were shown to be more susceptible for intestinal inflammation caused by C. rodentium that could be reversed by IL-22-Fc or IL-23 injections. The authors speculate that IL-23 was upstream of IL-22 signaling in this model, without providing any evidence.

Third, the authors switch to metabolic syndrome and observed that IL-22-Fc injection improves insulin sensitivity and blood glucose level.

Fourth, the authors suggest that IL-22-Fc injection improved symptoms of metabolic syndrome (weight loss, less food intake, increased gut barrier integrity, increased secretion of anorexic hormone PYY).

Finally, the authors showed that IL-22-Fc improved fat metabolism through its effect on liver cells and adipocytes.

However, experiments were complicated by the fact that IL-22KO and IL-22R1KO mice had different phenotype due to the fact that IL-22R1 can pair with other receptors (IL-10R2 and IL-20R2) and signal with IL-20 and IL-24.

In summary, the authors suggest that reduction of IL-23 driven IL-22 expression leads to alteration in proper fat metabolism in the liver cells and adipocytes, weakening of gut barrier integrity and chronic LPS presence in the blood stream, all resulting in obesity and metabolic syndrome development (insulin resistance).

Now, some thoughts to consider. First, are IL-22KO mice obese? Second, does injection of IL-23 rescue ob/ob mice on IL-22KO background?

David