Buck, M. D., Sowell, R. T., Kaech, S. M. & Pearce, E. L. Metabolic instruction of immunity. Cell 169, 570–586 (2017).
Man, K., Kutyavin, V. I. & Chawla, A. Tissue immunometabolism: development, physiology, and pathobiology. Cell Metab. 25, 11–26 (2017).
Geltink, R. I. K., Kyle, R. L. & Pearce, E. L. Unraveling the complex interplay between T cell metabolism and function. Annu. Rev. Immunol. 36, 461–488 (2018).
Michelet, X. et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat. Immunol. 19, 1330–1640 (2018).
Nicholas, D. A. et al. Fatty acid metabolites combine with reduced β-oxidation to activate Th17 inflammation in human type 2 diabetes. Cell Metab. 30, 447–461.e5 (2019).
Ringel, A. E. et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183, 1848–1866.e26 (2020).
Zhang, C. et al. STAT3 activation-induced fatty acid oxidation in CD8+ T effector cells is critical for obesity-promoted breast tumor growth. Cell Metab. 31, 148–161.e5 (2020).
Hersoug, L. G. & Linneberg, A. The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance? Allergy 62, 1205–1213 (2007).
Wenzel, S. E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 18, 716–725 (2012).
Zhang, A. & Silverberg, J. I. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J. Am. Acad. Dermatol. 72, 606–616.e4 (2015).
Fahy, J. V. Type 2 inflammation in asthma—present in most, absent in many. Nat. Rev. Immunol. 15, 57–65 (2015).
Bieber, T. Atopic Dermatitis. New Engl. J. Med. 358, 1483–1494 (2008).
Eckert, L. et al. The burden of atopic dermatitis in US adults: health care resource utilization data from the 2013 National Health and Wellness Survey. J. Am. Acad. Dermatol. 78, 54–61.e1 (2018).
Li, M. et al. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc. Natl Acad. Sci. USA 103, 11736–11741 (2006).
Leyva-Castillo, J. M. et al. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat. Commun. 4, 2847 (2015).
Swindell, W. R. et al. Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis. PLoS ONE 7, e34594 (2012).
Chiricozzi, A. et al. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J. Invest. Dermatol. 131, 677–687 (2011).
Hastie, A. T. et al. Baseline sputum eosinophil 1 neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort. J. Allergy Clin. Immunol. 146, 222–226 (2020).
Kuruvilla, M. E., Lee, F. E.-H. & Lee, G. B. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin. Rev. Allerg. Immuol. 56, 219–233 (2019).
Winer, S. et al. Obesity predisposes to Th17 bias. Eur. J. Immunol. 39, 2629–2635 (2009).
Endo, Y. et al. Obesity drives Th17 cell differentiation by inducing the lipid metabolic kinase ACC1. Cell Rep. 12, 1042–1055 (2015).
Manno, G. L. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
Bergen, V., Lange, M., Peidli, S., Wolf, F. A. & Theis, F. J. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat. Biotechnol. 38, 1408–1414 (2020).
Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2018).
McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https://doi.org/10.48550/arXiv.1802.03426 (2018).
Gooderham, M. J. et al. Dupilumab: A review of its use in the treatment of atopic dermatitis. J. Am. Acad. Dermatol. 78, S28–S36 (2018).
Hearn, A. P., Kent, B. D. & Jackson, D. J. Biologic treatment options for severe asthma. Curr. Opin. Immunol. 66, 151–160 (2020).
Tubau, C. & Puig, L. Therapeutic targeting of the IL-13 pathway in skin inflammation. Expert Rev. Clin. Immunol. 17, 15–25 (2021).
Laidlaw, T. M. et al. Dupilumab improves upper- and lower-airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann. Allergy Asthma Immunol. 126, 584–592.e1 (2021).
Rosen, E. D. & Spiegelman, B. M. PPARγ: a nuclear regulator of metabolism, differentiation, and cell growth. J. Biol. Chem. 276, 37731–37734 (2001).
Tontonoz, P. & Spiegelman, B. M. Fat and beyond: the diverse biology of PPARγ. Annu. Rev. Biochem. 77, 289–312 (2008).
Ahmadian, M. et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat. Med. 19, 557–566 (2013).
Lazar, M. A. Maturing of the nuclear receptor family. J. Clin. Invest. 127, 1123–1125 (2017).
Henriksson, J. et al. Genome-wide CRISPR screens in T helper cells reveal pervasive crosstalk between activation and differentiation. Cell 176, 882–896.e18 (2019).
Woerly, G. et al. Peroxisome proliferator-activated receptors α and γ down-regulate allergic inflammation and eosinophil activation. J. Exp. Med. 198, 411–421 (2003).
Honda, K., Marquillies, P., Capron, M. & Dombrowicz, D. Peroxisome proliferator–activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J. Allergy Clin. Immunol. 113, 882–888 (2004).
Hammad, H. et al. Activation of peroxisome proliferator-activated receptor-γ in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am. J. Pathol. 164, 263–271 (2004).
Lee, K. S. et al. Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor γ in a murine model of toluene diisocyanate-induced asthma. J. Immunol. 177, 5248–5257 (2006).
Chen, T. et al. PPAR-γ promotes type 2 immune responses in allergy and nematode infection. Sci. Immunol. 2, eaal5196 (2017).
Nobs, S. P. et al. PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation. J. Exp. Med. 214, 3015–3035 (2017).
Stark, J. M., Tibbitt, C. A. & Coquet, J. M. The metabolic requirements of Th2 cell differentiation. Front. Immunol. 10, 2318 (2019).
Klotz, L. et al. The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J. Exp. Med. 206, 2079–2089 (2009).
Bapat, S. P. et al. Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature 528, 137–141 (2015).
NCD-RisC. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016).
The GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 377, 13–27 (2017).
Abarca-Gómez, L. et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).
Lucas, C. et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584, 463–469 (2020).
Liston, A. et al. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc. Natl Acad. Sci. USA 105, 11903–11908 (2008).
Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763–774 (2001).
He, W. Adipose-specific peroxisome proliferator-activated receptor knockout causes insulin resistance in fat and liver but not in muscle. Proc. Natl Acad. Sci. USA 100, 15712–15717 (2003).
Rubtsov, Y. P. et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28, 546–558 (2008).
Hastie, A. T. et al. Mixed sputum granulocyte longitudinal impact on lung function in the severe asthma research program. Am. J. Resp. Crit. Care 203, 882–892 (2021).
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
Traag, V. A., Waltman, L. & Eck, N. J. V. From Louvain to Leiden: guaranteeing well-connected communities. Sci. Rep. 9, 5233 (2019).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2012).
Trapnell, C. et al. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat. Biotechnol. 31, 46–53 (2012).
Roberts, A., Pimentel, H., Trapnell, C. & Pachter, L. Identification of novel transcripts in annotated genomes using RNA-seq. Bioinformatics 27, 2325–2329 (2011).
Cho, H. et al. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485, 123–127 (2012).