Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis

By Min-Woo Lee, J. Odegaard, Lata Mukundan, Yifu Qiu, Ari B. Molofsky, J. Nussbaum, K. Yun, R. Locksley, A. Chawla. Cell, 2014

641 citations recorded by the source corpus.

SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7faa21c43e6338a4d991e87ceb9a83fbdd5a1814

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Artis
2. H. Spits
3. Andrew N. J. McKenzie
4. G. Eberl
5. A. Diefenbach
6. M. Colonna
7. I. Junttila
8. B. Spiegelman

Citations in the corpus

• Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes (2018, positive): “Several reports have established the ILC2-derived IL-13 acting on target cells via type II IL-4 receptor as a mechanism for several physiological functions such as beige fat biogenesis (38) or hepatic fibrosis (39) but if ILC2-derived IL-13 can act on autocrine manner has not been established.”
• Innate Lymphoid Cells: 10 Years On. (2018, positive): “For example, their production of IL-4 and IL-13 is reported to induce pre-adipocyte differentiation into beige adipocytes (Lee et al., 2015).”
• Innate Lymphoid Cells: a new paradigm in immunology (2015, background): “Last, IL-4 and IL-13 induce the differentiation of adipocyte precursors directly into beige fat (14).”
• Adipose tissue plasticity in health and disease (2022, background): “…through two proposed pathways: (1) the production of methi-onine-enkephalin peptides, which act on adipocytes to stimulate UCP1expression(Brestoffetal.,2015);and(2)theinductionofIL-4 and IL-13, which act on adipocyte progenitor cells to promote beige-adipocyte differentiation (Lee et al., 2015).”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “…including (1) increasing the production of Met-enkephalin peptides by ILC2s, which acts on adipocytes (Brestoff et al., 2015); and (2) stimulating IL4 secretion by eosinophils, which acts to promote the proliferation and beige differentiation of adipogenic precursor cells (Lee et al., 2015a).”