Macrophages participate in IL‐17‐mediated inflammation
Open accessAbstract
The involvement of macrophages (MΦs) in Th17‐cell responses is still poorly understood. While neutrophils are thought to be the predominant effector of Th17‐cell responses, IL‐17 is also known to induce myelotropic chemokines and growth factors. Other T‐cell‐derived cytokines induce non‐classical functions, suggesting that IL‐17 sigxnaling may similarly elicit unique MΦ functions. Here, we characterized the expression of subunits of the IL‐17 receptor on primary murine MΦs from different anatomical compartments. The greatest expression of IL‐17 receptors was observed on mucosal Ly6C hi "inflammatory" MΦs. We further observed upregulation of IL‐17 receptors in vitro on bone marrow‐derived macrophages (BMMΦs) in response to peptidoglycan or CpG oligonucleotide stimuli, and in vivo, upon CFA administration. Macrophages expressing IL‐17 receptors were observed infiltrating the hearts of mice with myocarditis, and genetic ablation of IL‐17RA altered MΦ recruitment. Treating primary MΦs from a wide variety of different anatomic sources (as well as cell lines) with IL‐17A induced the production of unique profiles of cytokines and chemokines, including GM‐CSF, IL‐3, IL‐9, CCL4/MIP‐1β and CCL5/RANTES. IL‐17A also induced production of IL‐12p70; IL‐17‐signaling‐deficient MΦs elicited diminished IFN‐γ production by responding DO11.10 CD4 + T cells when used as APCs. These data indicate that MΦs from different anatomic locations direct IL‐17‐mediated responses.
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The immune response (dominant macrophages with fewer T cells) is typical of EAM, autoimmune CVB3 myocarditis, and human myocarditis in males.
“This immune response (ie, dominant macrophages with fewer T cells) is typical of EAM, autoimmune CVB3 myocarditis, and human myocarditis in males (Figure 2). 182,184,185”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [185]
The Results and Discussion (page unavailable) say that macrophages and monocytes form the majority of inflammatory infiltrates in mouse experimental autoimmune myocarditis, supporting the EAM portion. The copy does not establish that this pattern is typical of autoimmune CVB3 myocarditis or human myocarditis in males; searches for those populations found no supporting passage. (LLM, conf=0.87)
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Cites
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · cited 1× · see citing works
“The prototypic proinflammatory cytokine of the IL17 family, IL17A, defines a novel CD4+ subset, the Th17 lineage [1, 2].”
BackgroundStructure and signalling in the IL-17 receptor family
Gaffen, S. L. (2009) · Nature reviews. Immunology · doi:10.1038/nri2586 · Cited by 1,475 · see citing works
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289 · see citing works
Macrophage Polarization Comes of Age
Mantovani, Sica, & Locati, M. (2005) · Immunity · doi:10.1016/j.immuni.2005.10.001 · Cited by 1,259 · cited 3× · see citing works
“In addition, phenotypic and functional diversity in the macrophage lineages have only recently begun to be widely appreciated [8, 9, 22].”
BackgroundKang, Z., Altuntas, C. Z., Gulen, M. F., Liu, C., Giltiay, N., Qin, H., Liu, L., Qian, W., Ransohoff, R. M., Bergmann, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.03.004 · Cited by 297 · see citing works
Flagged first, then by citations
Research works printed but not linked: 38
- [2]Harrington LE Hatton RD Mangan PR Turner H Murphy TL Murphy KM Weaver CT Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages Nature immunology 2005 6 1123 1132 16200070
- [4]Korn T Bettelli E Oukka M Kuchroo VK IL-17 and Th17 Cells Annual Review of Immunology 2009 27 485 517 19132915
- [5]Kolls JK Linden A Interleukin-17 family members and inflammation Immunity 2004 21 467 476 15485625
- [6]Ouyang W Kolls JK Zheng Y The biological functions of T helper 17 cell effector cytokines in inflammation Immunity 2008 28 454 467 18400188 PMC3424508
- [7]Schmidt-Weber CB Akdis M Akdis CA TH17 cells in the big picture of immunology J Allergy Clin Immunol 2007 120 247 254 17666214
- [8]Gordon S Alternative activation of macrophages Nat Rev Immunol 2003 3 23 35 12511873
- [10]Geissmann F Jung S Littman DR Blood monocytes consist of two principal subsets with distinct migratory properties Immunity 2003 19 71 82 12871640
- [11]Gordon S Taylor PR Monocyte and macrophage heterogeneity Nat Rev Immunol 2005 5 953 964 16322748
- [13]Ye P Rodriguez FH Kanaly S Stocking KL Schurr J Schwarzenberger P Oliver P Huang W Zhang P Zhang J Shellito JE Bagby GJ Nelson S Charrier K Peschon JJ Kolls JK Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense The Journal of experimental medicine 2001 194 519 527 11514607 PMC2193502
- [14]Cihakova D Sharma RB Fairweather D Afanasyeva M Rose NR Animal models for autoimmune myocarditis and autoimmune thyroiditis Methods Mol Med 2004 102 175 193 15286386
- [15]Pummerer CL Luze K Grassl G Bachmaier K Offner F Burrell SK Lenz DM Zamborelli TJ Penninger JM Neu N Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice J Clin Invest 1996 97 2057 2062 8621795 PMC507280
- [16]Afanasyeva M Georgakopoulos D Belardi DF Ramsundar AC Barin JG Kass DA Rose NR Quantitative analysis of myocardial inflammation by flow cytometry in murine autoimmune myocarditis: correlation with cardiac function Am J Pathol 2004 164 807 815 14982835 PMC1613271
- [17]Ely LK Fischer S Garcia KC Structural basis of receptor sharing by interleukin 17 cytokines Nat Immunol 2009 10 1245 1251 19838198 PMC2783927
- [19]Afanasyeva M Georgakopoulos D Rose NR Autoimmune myocarditis: cellular mediators of cardiac dysfunction Autoimmun Rev 2004 3 476 486 15546794
- [20]Baldeviano GC Barin JG Talor MV Srinivasan S Bedja D Zheng D Gabrielson K Iwakura Y Rose NR Cihakova D Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy Circ Res 106 1646 1655 20378858
- [21]Fleetwood AJ Lawrence T Hamilton JA Cook AD Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation J Immunol 2007 178 5245 5252 17404308
- [22]Mosser DM Edwards JP Exploring the full spectrum of macrophage activation Nat Rev Immunol 2008 8 958 969 19029990 PMC2724991
- [23]Rong Z Wang A Li Z Ren Y Cheng L Li Y Wang Y Ren F Zhang X Hu J Chang Z IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling Cell Res 2009 19 208 215 19079364 PMC4603938
- [24]Rickel EA Siegel LA Yoon BR Rottman JB Kugler DG Swart DA Anders PM Tocker JE Comeau MR Budelsky AL Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities J Immunol 2008 181 4299 4310 18768888
- [25]Das Sarma J Ciric B Marek R Sadhukhan S Caruso ML Shafagh J Fitzgerald DC Shindler KS Rostami A Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis J Neuroinflammation 2009 6 14 19400960 PMC2689857
- [26]Takayanagi H Osteoimmunology and the effects of the immune system on bone Nat Rev Rheumatol 2009 5 667 676 19884898
- [27]Janeway CA Jr Medzhitov R Innate immune recognition Annu Rev Immunol 2002 20 197 216 11861602
- [28]Shen F Hu Z Goswami J Gaffen SL Identification of common transcriptional regulatory elements in interleukin-17 target genes J Biol Chem 2006 281 24138 24148 16798734
- [29]Yang JH Sakamoto H Xu EC Lee RT Biomechanical regulation of human monocyte/macrophage molecular function Am J Pathol 2000 156 1797 1804 10793091 PMC1876939
- [30]Mosser DM Zhang X Activation of murine macrophages Curr Protoc Immunol 2008 Chapter 14 Unit 14 12 PMC2822273 19016446
- [31]Davies JQ Gordon S Isolation and culture of murine macrophages Methods Mol Biol 2005 290 91 103 15361657
- [32]Zhang X Goncalves R Mosser DM The isolation and characterization of murine macrophages Curr Protoc Immunol 2008 Chapter 14 Unit 14 11 PMC2834554 19016445
- [33]Zhu S Pan W Shi P Gao H Zhao F Song X Liu Y Zhao L Li X Shi Y Qian Y Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signaling J Exp Med 207 2647 2662 21078888 PMC2989772
- [34]Sutton CE Lalor SJ Sweeney CM Brereton CF Lavelle EC Mills KH Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity Immunity 2009 31 331 341 19682929
- [35]Martin B Hirota K Cua DJ Stockinger B Veldhoen M Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals Immunity 2009 31 321 330 19682928
- [36]Lockhart E Green AM Flynn JL IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection J Immunol 2006 177 4662 4669 16982905
- [37]Michel ML Mendes-da-Cruz D Keller AC Lochner M Schneider E Dy M Eberl G Leite-de-Moraes MC Critical role of ROR-gammat in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation Proc Natl Acad Sci U S A 2008 105 19845 19850 19057011 PMC2604995
- [38]Da Silva CA Hartl D Liu W Lee CG Elias JA TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation J Immunol 2008 181 4279 4286 18768886 PMC2577310
- [39]Lin Y Ritchea S Logar A Slight S Messmer M Rangel-Moreno J Guglani L Alcorn JF Strawbridge H Park SM Onishi R Nyugen N Walter MJ Pociask D Randall TD Gaffen SL Iwakura Y Kolls JK Khader SA Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis Immunity 2009 31 799 810 19853481 PMC2789998
- [41]Toy D Kugler D Wolfson M Vanden Bos T Gurgel J Derry J Tocker J Peschon J Cutting edge: interleukin 17 signals through a heteromeric receptor complex J Immunol 2006 177 36 39 16785495
- [42]Wright JF Bennett F Li B Brooks J Luxenberg DP Whitters MJ Tomkinson KN Fitz LJ Wolfman NM Collins M Dunussi-Joannopoulos K Chatterjee-Kishore M Carreno BM The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex J Immunol 2008 181 2799 2805 18684971
- [43]Kuestner RE Taft DW Haran A Brandt CS Brender T Lum K Harder B Okada S Ostrander CD Kreindler JL Aujla SJ Reardon B Moore M Shea P Schreckhise R Bukowski TR Presnell S Guerra-Lewis P Parrish-Novak J Ellsworth JL Jaspers S Lewis KE Appleby M Kolls JK Rixon M West JW Gao Z Levin SD Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F J Immunol 2007 179 5462 5473 17911633 PMC2849293
- [44]Livak KJ Schmittgen TD Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods 2001 25 402 408 11846609
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- Authors
- Barin, J. G., Baldeviano, G. C., Talor, M. V., Wu, L., Ong, S., Quader, F., Chen, P., Zheng, D., Caturegli, P., Rose, N. R., & C̆iháková, D.
- Affiliations
- Johns Hopkins University (US)
- Shanghai Medical College of Fudan University (CN)
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2012-01-23
- Volume
- 42
- Issue
- 3
- Pages
- 726-736
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- PMC
- PMC4292791
- OpenAlex
- W1983260461
- Cited by
- 120
- References
- 6
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 5 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 4
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL087033, R01HL067290, R01HL113008, R01 HL67290, R01HL070729, HL087033, R01 HL 70729)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- macrophages, IL-17, IL-17 receptor, Th17 cells, inflammatory macrophages, IL-17RA, macrophage recruitment, myocarditis, cytokine and chemokine production, GM-CSF, CCL5/RANTES, IL-12p70, interferon-gamma, antigen-presenting cells, bone marrow-derived macrophages, peptidoglycan, CpG oligodeoxynucleotides, CFA, autoimmunity
- MeSH terms
- Animals, Female, Flow Cytometry, Inflammation, Macrophage Activation, Macrophages, Mice, Inbred BALB C, Myocarditis, Specific Pathogen-Free Organisms, Up-Regulation, Mice, Knockout, Chemokines, Interleukin-17, Mice, Receptors, Interleukin-17
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