IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake

IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake View ORCID Profile Jillian Yong Xin Sieh , View ORCID Profile Gabriel Osborn , View ORCID Profile Sophia N. Karagiannis , View ORCID Profile Francesca Capon doi: https://doi.org/10.1101/2025.10.22.683795 Jillian Yong Xin Sieh 1 Department of Medical and Molecular Genetics , King’s College London, London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jillian Yong Xin Sieh Gabriel Osborn 2 St John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine , King’s College London, London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gabriel Osborn Sophia N. Karagiannis 2 St John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine , King’s College London, London, UK 3 Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King’s College London, Innovation Hub, Guy’s Cancer Centre , London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sophia N. Karagiannis For correspondence: sophia.karagiannis{at}kcl.ac.uk fcapon{at}cmmt.ubc.ca Francesca Capon 1 Department of Medical and Molecular Genetics , King’s College London, London, UK 4 BC Children’s Hospital Research Institute, Vancouver; Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Francesca Capon For correspondence: sophia.karagiannis{at}kcl.ac.uk fcapon{at}cmmt.ubc.ca Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Macrophages exhibit remarkable functional plasticity, adopting immune activating or immune suppressive states in response to environmental cues. While these phenotypic shifts are essential to immune homeostasis, the mechanisms whereby they are regulated in humans are poorly understood. Here, we investigated the role of interleukin (IL)-36γ, a barrier cytokine that is strongly induced in response to infection. We show that IL-36γ signalling modifies the anti-inflammatory phenotype of human alternatively activated (M2a) macrophages, by decreasing the expression the CD163 M2 marker. This change was accompanied by the upregulation of M1 surface markers (CD40, CD80) and M1 cytokines (e.g. TNFα, CXCL8). IL-36γ treatment of M2a macrophages also reduced the expression of TREM2 and CD36, two lipid-binding receptors that sustain the energy requirements of the M2 state. Accordingly, we also observed a decrease in the uptake of CD36 and TREM2 ligands (oxidised low-density lipoproteins). These findings indicate that IL-36γ shifts the immune and metabolic profile of M2a macrophages towards an M1-like state. 1. Introduction Macrophages display remarkable functional plasticity and respond to environmental cues by adopting a variety of activation states. To reflect this diversity, macrophages are broadly classified into immune activating and immune suppressive populations. In-vitro, these are studied as M1 and M2 subsets. M1 macrophages have immune activating functions mediated by the production of inflammatory cytokines and the expression of T-cell co-stimulatory molecules. M2 macrophages can be further subdivided in M2a, M2b, M2c and M2d subsets, respectively contributing to tissue repair, immune regulation, resolution of inflammatory responses and tumour progression 1 . The balance between immune activating and immune suppressive populations is critical to tissue homeostasis, as demonstrated by the dysregulation of macrophage states in chronic inflammatory disease and cancer 1 . While targeting macrophage polarisation has emerged as a new strategy for the treatment of these conditions, the factors that promote macrophage phenotype shifts in humans are not fully understood. Interleukin (IL)-36α, IL-36β, and IL-36γ (IL-36) are closely related members of the IL-1 cytokine family. They bind a common receptor that consists of a signalling subunit (IL-36R) and an accessory co-receptor (IL-1RAcP). IL-36 is primarily expressed in skin, lung, and gut, where it is rapidly induced following microbial challenge or tissue injury. Engagement of IL-36R then triggers canonical NF-κB and MAPK signalling, resulting in the release of pro-inflammatory cytokines and chemokines, which recruit and activate myeloid and lymphoid cells 2 . IL-36 amplifies innate and adaptive immune responses. In the skin, it promotes keratinocyte activation and antiviral responses 3 . In the gut, it strengthens mucosal defences by upregulating antimicrobial peptide production 4 . Finally, IL-36 enhances responses to infection and inflammatory stimuli in the lung, while also contributing to tissue injury 5 . In all barrier sites, IL-36 upregulates dendritic cell activity, thus promoting the polarisation of T cells towards Th1 and Th17 phenotypes 6 , 7 . Given these proinflammatory functions, we hypothesised that IL-36 can shift M2 macrophages towards an M1-like state. We have therefore explored the effects of the cytokine on macrophage surface markers and cytokine production. 2. Materials and Methods 2.1 Generation and Stimulation of Human Monocyte-Derived Macrophages Leukocyte-enriched cones obtained from healthy donors were purchased from the NHS Blood and Transplant Service (Tooting, UK) and Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque™ PLUS (Cytiva). Monocytes were then extracted from freshly isolated PBMCs with the Pan Monocyte Isolation Kit (Miltenyi Biotec). Macrophages were differentiated and polarised as previously described 8 . Briefly, monocytes were grown in complete medium (RPMI 1640-GlutaMAX™ supplemented with 10% FBS and 1% penicillin-streptomycin) containing 50 ng/mL M-CSF for four or five days. Cells were then polarised by adding complete medium supplemented with 16.7 ng/mL M-CSF and with the agents required for M1 (100 ng/mL LPS (Merck) + 40 ng/mL IFN-γ (Thermo Fisher Scientific)), M2a (20 ng/mL IL-4 (PeproTech)) or M2c (20 ng/mL IL-10 (PeproTech)) polarization. After 24 hours, cells were treated with 50 ng/mL of recombinant human IL-36γ (Bio-Techne) in complete medium. Cells were harvested after 6 or 24 hours. Cells were harvested at 6 hours for real-time qPCR to examine gene expression changes and at 24 hours for flow cytometry to assess surface marker expression. 2.2 Flow Cytometry Macrophages were incubated with 10 μg/mL human Fc block (BD Biosciences) for 10 minutes at room temperature. Cells were then stained on ice for 30 minutes with fluorochrome-conjugated antibodies (Table S1) and for another 30-minute with LIVE/DEAD™ Fixable Near-IR Dead Cell Stain (Invitrogen). Cells were acquired using a CytoFLEX flow cytometer and the data was analysed using FlowJo (BD Biosciences, v10.9.0). 2.3 Real Time PCR and ELISA Total mRNA was extracted from macrophages using the RNeasy Mini Kit (QIAGEN) and reverse-transcribed into cDNA with a High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems). Real-time PCR was performed using the PowerUp™ SYBR™ Green Master Mix (Applied Biosystems) with primers for target and housekeeping ( GAPDH ) genes (sequences in Table S2). TNF-α and IL-8 were measured with the Human TNF-alpha Quantikine ELISA Kit (Bio-Techne) and Human IL-8 Quantikine ELISA Kit (Bio-Techne). 2.4 Measurement of Oxidized Low-Density Lipoproteins (oxLDL) Uptake Human monocyte-derived macrophages were incubated at 37°C for 30 minutes in serum-free RPMI 1640-GlutaMAX™ containing 5 μg/mL DiI-conjugated human oxLDL (Thermo Fisher Scientific). oxLDL uptake was then quantified using a CytoFlex flow cytometer (Beckman Coulter), with detection of DiI fluorescence in the PE channel. A positive control was included by exposing cells to DiI-oxLDL for 24 hours. The data was analysed using FlowJo (BD Biosciences, v10.9.0). 2.5 Statistical Analysis Comparisons between two independent groups were undertaken with Student’s unpaired t-test or the Mann-Whitney U test, as applicable. Comparisons between multiple independent groups were undertaken using one-way ANOVA with Tukey’s post-hoc test. The analysis of paired samples was implemented with Student’s paired t-test or Wilcoxon signed-rank test. When multiple paired comparisons were performed at the same time, a Bonferroni-Dunn correction was applied. P-values <0.05 were considered significant. 3. Results and Discussion To recapitulate the functional extremes of macrophage plasticity, we differentiated human monocytes into pro-inflammatory (M1), tissue remodelling (M2a), and immune-regulatory (M2c) subsets (Fig. S1). We then assessed IL-36R expression on these cells. We found that the proportion of IL-36R–positive cells was higher in M2a (90.7%) compared to M2c (68.8%) and M1 (55.9%) macrophages ( Fig. 1a ). Consistently, IL-36R mean fluorescence intensity (MFI) was highest in M2a macrophages ( Fig. 1a ). This population may therefore be particularly sensitive to the effects of IL-36 cytokines. Download figure Open in new tab Fig.1 IL-36γ treatment shifts human M2a macrophages towards an M1 state. (a) (Left) Representative flow cytometry plots and bar plots showing the percentage of cells expressing IL-36R, gated on singlet live CD14+ cells. (Right) Representative flow cytometry histograms and bar plots showing the MFI of IL-36R in each subset. **P<0.01 (One-way ANOVA with Tukey’s post-hoc test). (b-c) Representative flow cytometry histograms (left) and paired dot plots (right) showing that IL-36γ treatment of monocyte-derived macrophages affects the expression of M1 (b) and M2 (c) markers *P<0.05, ***P<0.001, ****P<0.0001 (paired t-tests followed by Bonferroni-Dunn correction). We next investigated how macrophage polarisation is affected by IL-36γ, the cytokine isoform that is most abundantly expressed in barrier tissues 2 . We specifically examined the effects IL-36γ on M2a and M2c macrophages, including the M1 subset as a reference for a proinflammatory state. We found that cytokine treatment had no significant effects on M2c cells. Conversely, we observed that in M2a macrophages, IL-36γ significantly up-regulated M1-associated molecules, including CD40 (1.34-fold, P<0.05) and CD80 (1.64-fold, P<0.001) ( Fig. 1b ). Meanwhile the analysis of M2 markers showed that IL-36γ induced modest increase in CD206 MFI (1.09-fold, P<0.05), but a pronounced reduction in CD163 expression (0.89-fold, P<0.0001) ( Fig. 1c ). To further investigate these findings, we examined the effects of IL-36γ on two additional proteins associated with M2 states, i.e. the TREM2 and CD36 lipid receptors 1 . We observed that both were significantly downregulated following IL-36γ treatment (TREM2: 0.76-fold, P<0.05; CD36: 0.92-fold, P<0.05) ( Fig. 1c ). Accordingly, we found that the uptake of oxidized low-density lipoprotein (a TREM2 and CD36 ligand) was significantly reduced in M2a macrophages that had been pre-treated with IL-36γ (0.90-fold, P<0.01) ( Fig. 2a ). Thus, IL-36γ upregulates M1 markers in M2a macrophages, while downregulating canonical and non-canonical M2 markers. Download figure Open in new tab Fig.2 IL-36γ treatment affects lipid uptake and cytokine expression in human M2a macrophages. (a) Representative flow cytometry histogram (left) and paired dot plots (right) showing that IL-36γ treatment of M2a macrophages affects oxLDL uptake. (b-c) Paired dot plots showing the effect of IL-36γ on the mRNA expression of M2 (b) and M1 (c) cytokines. Gene expression was measured by real-time qPCR, using GAPDH as a housekeeping gene. (d) Paired dot plots showing the effect of IL-36γ on TNF-α and CXCL8 protein production. Data for untreated M1 macrophages is included in all plots as a reference for a pro-inflammatory state. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 (paired t-test; a Bonferroni-Dunn correction was applied in b-d). To further validate the phenotypic shift towards a pro-inflammatory state, we examined the effects of IL-36γ on M2 cytokine production. We found that IL-36γ treatment modestly up-regulated the mRNA expression of CCL17 (2.4-fold; P<0.0001) and CCL22 (1.4-fold; P<0.01), while downregulating IL10 (1.8-fold, P<0.01) ( Fig. 2b ). Conversely, IL-36γ induced a substantial increase in the expression of M1 cytokine genes, including TNFA (5.0-fold; P<0.01), IL6 (10.9-fold; P<0.0001), CXCL8 (8.5-fold; P<0.01), CXCL9 (2.1-fold; P<0.01) and CXCL10 (1.8-fold; P<0.05) ( Fig. 2c ). Follow-up ELISAs of TNF and CXCL8 confirmed that IL-36γ increases the release of these two key M1 mediators (TNF: 3.0-fold, CXCL8 6.1-fold; P<0.05 for both) ( Fig. 2d ). Thus, the pro-inflammatory shift induced by IL-36γ treatment of M2a macrophages is also reflected in an increase production of M1 cytokines. Earlier studies have demonstrated that IL-36 can activate NF-κB signalling and upregulate cytokine production in human macrophages 9 , 10 . Here, we build on these findings to systematically investigate the pro-inflammatory shifts induced by IL-36 treatment of human tissue-remodelling (M2a) and immune-regulatory (M2c) macrophages. We found that IL-36γ polarised M2a macrophages towards an M1-like phenotype. This was evident at the surface marker level, as IL-36γ upregulated the expression of CD40 and CD80, while downregulating that of CD163, TREM2, and CD36. The changes in cytokine production further supported this shift, with IL-36γ strongly inducing TNFα, IL-6, and CXCL8. In this context, the modest induction of CCL17 and CCL22 suggests that IL-36γ does not repolarise M2a macrophages but rather reshapes their profile towards a mixed state enriched in pro-inflammatory mediators. We observed that the downregulation of TREM2 and CD36 was accompanied by a reduced lipoprotein (oxLDL) uptake. Of note, the lysosomal degradation of lipoproteins generates fatty acids, one of the main sources of energy for M2 macrophages 11 . Given that the inhibition of fatty acid oxidation impairs M2 functions 11 , it is tempting to speculate that the effects of IL-36γ on lipid uptake may contribute to the proinflammatory shifts induced by the cytokine. Our study has some limitations. While we analysed the effects of IL-γ36 on critical surface markers and cytokines, we did not undertake transcriptomics studies that could have captured a broader spectrum of changes, including those affecting lipid metabolism genes. Likewise, we did not investigate how IL-36γ affects macrophage functions such as antigen presentation or T cell activation. As our experiments were restricted to an in vitro system, future work should investigate the role of IL-36γ in shaping macrophage phenotypes in disease settings. In fact, excessive IL-36 activity has been implicated in inflammatory conditions (e.g. psoriasis, inflammatory bowel disease and pulmonary fibrosis) characterised by dysregulated macrophage polarization 2 , 12 . Conversely, IL-36 signalling has a protective role in some cancers (e.g. lung squamous cell carcinoma 13 ) where the abundance of TREM2+ macrophages correlates with a poor prognosis 14 . Further studies should therefore investigate the potential of modulating IL-36γ signalling to reprogramme macrophage responses in different disease contexts. Competing interest statement FC has received grant funding and consultancy fees from Boehringer Ingelheim. SNK is founder and shareholder of Epsilogen Ltd. Author Contributions FC, SNK and JYXS designed the study. JYXS performed the experiments with GO. JYXS and FC wrote the manuscript. FC and SNK supervised the study. All authors have reviewed and agreed to the final manuscript. Funding This research was funded and supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. This research was also supported by the King’s Health Partners Centre for Translational Medicine. This report is independent research. NHS Blood & Transplant have provided material in support of the research. The authors acknowledge funds from the UK Medical Research Council (MR/N013700/1) a King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences and Cancer Research UK (C30122/A11527; C30122/A15774). JYXS’ PhD scholarship was funded by the NIHR BRC at Guy’s and St. Thomas’ NHS Foundation Trust, in partnership with King’s College London. FC is supported by the BC Leading Edge Endowment Fund. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, King’s Health Partners, NIHR, the Department of Health or NHS Blood & Transplant. None of the funders had any influence in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Funder Information Declared Medical Research Council, https://ror.org/03x94j517 , MR/N013700/1 Cancer Research UK , C30122/A11527 , C30122/A15774 References ↵ Guan F , Wang R , Yi Z et al. Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets . Signal Transduct Target Ther 2025 ; 10 : 93 . OpenUrl PubMed ↵ Sugiura K , Fujita H , Komine M et al. The role of interleukin-36 in health and disease states . Journal of the European Academy of Dermatology and Venereology: JEADV 2024 ; 38 : 1910 – 25 . OpenUrl ↵ Wang P , Gamero AM , Jensen LE . IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-alpha/beta in IRF1 dependent and independent manners . Nature communications 2019 ; 10 : 4700 . OpenUrl PubMed ↵ Ngo VL , Abo H , Maxim E et al. A cytokine network involving IL-36gamma, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage . Proc Natl Acad Sci U S A 2018 ; 115 : E5076 – E85 . OpenUrl Abstract / FREE Full Text ↵ Zhang J , Yin Y , Lin X et al. IL-36 induces cytokine IL-6 and chemokine CXCL8 expression in human lung tissue cells: Implications for pulmonary inflammatory responses . Cytokine 2017 ; 99 : 114 – 23 . OpenUrl CrossRef PubMed ↵ Carrier Y , Ma HL , Ramon HE et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis . J Invest Dermatol 2011 ; 131 : 2428 – 37 . OpenUrl CrossRef PubMed Web of Science ↵ Vigne S , Palmer G , Martin P et al. IL-36 signaling amplifies Th1 responses by enhancing proliferation and Th1 polarization of naive CD4+ T cells . Blood 2012 ; 120 : 3478 – 87 . OpenUrl Abstract / FREE Full Text ↵ Pellizzari G , Hoskin C , Crescioli S et al. IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states . EBioMedicine 2019 ; 43 : 67 – 81 . OpenUrl PubMed ↵ Dietrich D , Martin P , Flacher V et al. Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines . Cytokine 2016 ; 84 : 88 – 98 . OpenUrl CrossRef PubMed ↵ Kovach MA , Che K , Brundin B et al. IL-36 Cytokines Promote Inflammation in the Lungs of Long-Term Smokers . Am J Respir Cell Mol Biol 2021 ; 64 : 173 – 82 . OpenUrl PubMed ↵ Yan J , Horng T. Lipid Metabolism in Regulation of Macrophage Functions . Trends in cell biology 2020 ; 30 : 979 – 89 . OpenUrl CrossRef PubMed ↵ Sachen KL , Arnold Greving CN , Towne JE . Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions . Cytokine 2022 ; 156 : 155897 . OpenUrl CrossRef PubMed ↵ Wang X , Zhao X , Feng C et al. IL-36gamma Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses . Cancer Cell 2015 ; 28 : 296 – 306 . OpenUrl CrossRef PubMed ↵ Zhang H , Liu Z , Wen H et al. Immunosuppressive TREM2(+) macrophages are associated with undesirable prognosis and responses to anti-PD-1 immunotherapy in non-small cell lung cancer . Cancer immunology, immunotherapy: CII 2022 ; 71 : 2511 – 22 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted October 23, 2025. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake Jillian Yong Xin Sieh , Gabriel Osborn , Sophia N. Karagiannis , Francesca Capon bioRxiv 2025.10.22.683795; doi: https://doi.org/10.1101/2025.10.22.683795 Share This Article: Copy Citation Tools IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake Jillian Yong Xin Sieh , Gabriel Osborn , Sophia N. Karagiannis , Francesca Capon bioRxiv 2025.10.22.683795; doi: https://doi.org/10.1101/2025.10.22.683795 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Immunology Subject Areas All Articles Animal Behavior and Cognition (7635) Biochemistry (17697) Bioengineering (13895) Bioinformatics (41951) Biophysics (21456) Cancer Biology (18594) Cell Biology (25520) Clinical Trials (138) Developmental Biology (13381) Ecology (19903) Epidemiology (2067) Evolutionary Biology (24323) Genetics (15612) Genomics (22510) Immunology (17737) Microbiology (40401) Molecular Biology (17183) Neuroscience (88622) Paleontology (667) Pathology (2833) Pharmacology and Toxicology (4825) Physiology (7644) Plant Biology (15158) Scientific Communication and Education (2046) Synthetic Biology (4296) Systems Biology (9825) Zoology (2271)