Wednesday, March 18, 2015

IL-33 links innate lymphoid cells group 2 to lean body mass control

There is one aspect of immune system that I did not get at all. It is related to the role of immune system in maintaining a lean body mass by controlling browning [beiging] of white adipose tissue and increasing energy expenditure.

Previous studies have implicated immune cells, such as eosinophils, type 2 macrophages and IL-4rα signalling in body energy expenditure and lean body mass control. New study in journal Nature has provided evidence suggesting that type 2 innate lymphoid cells, ILC2 and IL-33 play an independent and non-redundant role in lean body mass control and energy expenditure

The authors showed that in both human and mouse, white adipose tissue contain LinIL-25IL-127+population expressing IL-33R typical for ILC2. The frequency and number of ILC2 population in white adipose tissue were inversely correlated with obesity or high fat diet.

Experiments with IL-33KO mice or recombinant mouse IL-33 showed that ILC2 population in white adipose tissue retracted or expanded depending on presence of IL-33.

Adipose tissue analysis revealed that IL-33 induced UCP1 expression in white adipose tissue. UCP1 is responsible for high energy expenditure in beige fat.

Adoptive transfer of ILC2 into ILC2-deficient hosts showed that IL-33 worked through ILC2. Additional experiments revealed that IL-33/ILC2 axis worked independently from eosinophils, regulatory T cells or IL-4rα signalling.

Somewhat similar results were presented in another paper published in journal Cell earlier this year. However, in that paper the authors observed that eosinophils and IL-4rα signalling were also involved alongside with IL-33/ILC2. It would be interesting to know what is the reason for this discrepancy.

In summary, these results points to a novel function of innate immune system. Though It may even nothing to do with immune function per se but rather linking ancient metabolic pathways to innate immune cells. Even if IL-33 can help to reduce body fat, it does not necessarily means that we could start injecting obese people with IL-33. IL-33 has been implicated in pathological responses as well, like asthma or allergy. Only global view of cytokine function could tell us the real usefulness of any finding. Discrete, individual disease models are insufficient for this task and could lead to wrong conclusions. 

David Usharauli

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