Sunday, December 13, 2015

IL-22 promotes intestinal integrity via direct effect on stem cells

Initially, the authors showed that IL-22 produced by group 3 innate lymphoid cells (ILC3) promoted in vitro growth of intestinal organoids (small intestine crypt cells cultured with EGF, Noggin and R-spondin-1, ENR).

Growth augmentation by IL-22 was mediated via STAT3 signaling, as shown by growth defect of STAT3 KO crypt cells cultured with IL-22.

Unlike Paneth cell depletion, experiments with  Lrg5+ stem cell depletion confirmed that IL-22 promoted intestinal regeneration via its effect on stem cells (though I don't know whether organoids growth could happen without  Lrg5+ cells, in the first place).

Finally, the authors conducted in vivo experiments with rh IL-22 to validate hypothesis that IL-22 or its analog could improve survival in GvHD (condition that leads to intestinal damage). Indeed, treatment of mice with stabilized rhIL-22 analog, F-652, following bone marrow transplantation (BMT), reduced intestinal damage and improved host survival (though mrIL-22 effect was less dramatic in Fig 3).

In summary, this study suggests that IL-22 could provide therapeutic benefits in medical conditions where gut integrity is compromised.

Note: the authors claim that they filed a provisional patent application "on the use of ISC growth factor". I don't believe one could get any patent on naturally occurring products, such as IL-22. In addition, idea that IL-22 affects gut epithelia is well established concept. While the authors refined this concept and showed that IL-22 may work directly on stem cells, this by itself is not a patent-eligible innovation, in my view.

David Usharauli

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