518
Views
0
CrossRef citations to date
0
Altmetric
Original research

Loss of β2-integrin function results in metabolic reprogramming of dendritic cells, leading to increased dendritic cell functionality and anti-tumor responses

, , , , , , , , , , , & show all
Article: 2369373 | Received 03 Nov 2023, Accepted 13 Jun 2024, Published online: 21 Jun 2024

References

  • Bošnjak B, Kth D, Förster R, Hammerschmidt SI. Imaging dendritic cell functions*. Immunol Rev. 2021;306(1):137–18. doi:10.1111/imr.13050.
  • Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15(7):e257–e267. doi:10.1016/s1470-2045(13)70585-0.
  • Gardner A, de Mingo Pulido Á, Ruffell B. Dendritic Cells and Their Role in Immunotherapy. Front Immunol. 2020;11:924. doi:10.3389/fimmu.2020.00924.
  • Liu J, Zhang X, Cheng Y, Cao X. Dendritic cell migration in inflammation and immunity. Cell Mol Immunol. 2021;18(11):2461–2471. doi:10.1038/s41423-021-00726-4.
  • Winzler C, Rovere P, Rescigno M, Granucci F, Penna G, Adorini L, Zimmermann VS, Davoust J, Ricciardi-Castagnoli P. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med. 1997;185(2):317–328. doi:10.1084/jem.185.2.317.
  • Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, Pandey G, Leboeuf M, Elpek KG, Helft J. et al. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012;13(9):888–899. doi:10.1038/ni.2370.
  • Morrison VL, James MJ, Grzes K, Cook P, Glass DG, Savinko T, Lek HS, Gawden-Bone C, Watts C, Millington OR. et al. Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nat Commun. 2014;5(1). doi:10.1038/ncomms6359.
  • Everts B, Amiel E, van der Windt GJW, Freitas TC, Chott R, Yarasheski KE, Pearce EL, Pearce EJ. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood. 2012;120(7):1422–1431. doi:10.1182/blood-2012-03-419747.
  • Everts B, Amiel E, Huang S-C, Smith AM, Chang C-H, Lam WY, Redmann V, Freitas TC, Blagih J, van der Windt GJW. et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014;15(4):323–332. doi:10.1038/ni.2833.
  • O’Neill LAJ, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213(1):15–23. doi:10.1084/jem.20151570.
  • Liu D, Wu J, An J, Cyster JG. Requirements for cDC2 positioning in blood-exposed regions of the neonatal and adult spleen. J Exp Med. 2020;217(11):e20192300. doi:10.1084/jem.20192300.
  • Varga G, Balkow S, Wild MK, Stadtbaeumer A, Krummen M, Rothoeft T, Higuchi T, Beissert S, Wethmar K, Scharffetter-Kochanek K. et al. Active MAC-1 (CD11b/CD18) on DCs inhibits full T-cell activation. Blood. 2006;109(2):661–669. doi:10.1182/blood-2005-12-023044.
  • Ehirchiou D, Xiong Y, Xu G, Chen W, Shi Y, Zhang L. CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation. J Exp Med. 2007;204(7):1519–1524. doi:10.1084/jem.20062292.
  • Savinko TS, Morrison VL, Uotila LM, Wolff CHJ, Alenius HT, Fagerholm SC. Functional Beta2-Integrins Restrict Skin Inflammation in vivo. J Invest Dermatol. 2015;135(9):2249–2257. doi:10.1038/jid.2015.164.
  • Han C, Jin J, Xu S, Liu H, Li N, Cao X. Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating syk and promoting degradation of MyD88 and TRIF via cbl-b. Nat Immunol. 2010;11(8):734–742. doi:10.1038/ni.1908.
  • Leon F, Contractor N, Fuss I, Marth T, Lahey E, Iwaki S, la Sala A, Hoffmann V, Strober W, Kelsall BL. Antibodies to complement receptor 3 treat established inflammation in murine models of colitis and a novel model of psoriasiform dermatitis. J Immunol. 2006;177(10):6974–6982. doi:10.4049/jimmunol.177.10.6974.
  • D’Agata ID, Paradis K, Chad Z, Bonny Y, Seidman E. Leucocyte adhesion deficiency presenting as a chronic ileocolitis. Gut. 1996;39(4):605–608. doi:10.1136/gut.39.4.605.
  • Guenther C, Faisal I, Fusciello M, Sokolova M, Harjunpää H, Ilander M, Tallberg R, Vartiainen MK, Alon R, Gonzalez-Granado JM. et al. β2-integrin adhesion regulates dendritic cell epigenetic and transcriptional landscapes to restrict dendritic cell maturation and tumor rejection. Cancer Immunol Res. 2021;9(11):1354–1369. doi:10.1158/2326-6066.CIR-21-0094.
  • Guenther C, Faisal I, Uotila LM, Asens ML, Harjunpää H, Savinko T, Öhman T, Yao S, Moser M, Morris SW. et al. A β2-Integrin/MRTF-A/SRF pathway regulates dendritic cell gene expression, adhesion, and traction force generation. Front Immunol. 2019;10:1138. doi:10.3389/fimmu.2019.01138.
  • Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM. et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20(6):375–388. doi:10.1038/s41577-020-0285-6.
  • Helft J, Böttcher J, Chakravarty P, Zelenay S, Huotari J, Schraml BU, Goubau D, Reise, Reis e Sousa C, Sousa C. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity. 2015;42(6):1197–1211. doi:10.1016/j.immuni.2015.05.018.
  • Lawless SJ, Kedia-Mehta N, Walls JF, McGarrigle R, Convery O, Sinclair LV, Navarro MN, Murray J, Finlay DK. Glucose represses dendritic cell-induced T cell responses. Nat Commun. 2017;8(1):15620. doi:10.1038/ncomms15620.
  • Argüello RJ, Combes AJ, Char R, Gigan JP, Baaziz AI, Bousiquot E, Camosseto V, Samad B, Tsui J, Yan P. et al. SCENITH: A flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab. 2020;32(6):1063–1075.e7. doi:10.1016/J.CMET.2020.11.007.
  • Ponticos M, Lu QL, Morgan JE, Hardie DG, Partridge TA, Carling D. Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle. Embo J. 1998;17(6):1688–1699. doi:10.1093/emboj/17.6.1688.
  • Cytlak U, Resteu A, Bogaert D, Kuehn HS, Altmann T, Gennery A, Jackson G, Kumanovics A, Voelkerding KV, Prader S. et al. Ikaros family zinc finger 1 regulates dendritic cell development and function in humans. Nat Commun. 2018;9(1):1239. doi:10.1038/s41467-018-02977-8.
  • Boutboul D, Kuehn HS, Van de Wyngaert Z, Niemela JE, Callebaut I, Stoddard J, Lenoir C, Barlogis V, Farnarier C, Vely F. et al. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. J Clin Invest. 2018;128(7):3071–3087. doi:10.1172/JCI98164.
  • Oh K-S, Gottschalk RA, Lounsbury NW, Sun J, Dorrington MG, Baek S, Sun G, Wang Z, Krauss KS, Milner JD. et al. Dual roles for Ikaros in regulation of macrophage chromatin state and inflammatory gene expression. J Immunol. 2018;201(2):757–771. doi:10.4049/jimmunol.1800158.
  • Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343(6168):301–305. doi:10.1126/science.1244851.
  • Wang F, Zhang S, Vuckovic I, Jeon R, Lerman A, Folmes CD, Dzeja PP, Herrmann J. Glycolytic stimulation is not a requirement for M2 Macrophage differentiation. Cell Metab. 2018;28(3):463–475.e4. doi:10.1016/j.cmet.2018.08.012.
  • Du H, Bartleson JM, Butenko S, Alonso V, Liu WF, Winer DA, Butte MJ. Tuning immunity through tissue mechanotransduction. Nat Rev Immunol. 2023;23(3):174–188. doi:10.1038/s41577-022-00761-w.
  • Griffiths KL, Tan JKH, O’Neill HC. Characterization of the effect of LPS on dendritic cell subset discrimination in spleen. J Cell Mol Med. 2014;18(9):1908–1912. doi:10.1111/jcmm.12332.
  • West MA, Wallin RPA, Matthews SP, Svensson HG, Zaru R, Ljunggren H-G, Prescott AR, Watts C. Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science. 2004;305(5687):1153–1157. doi:10.1126/science.1099153.
  • Joshi I, Yoshida T, Jena N, Qi X, Zhang J, Van Etten RA, Georgopoulos K. Loss of ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia. Nat Immunol. 2014;15(3):294–304. doi:10.1038/ni.2821.
  • Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V. et al. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature. 2017;542(7642):479–483. doi:10.1038/NATURE21076.
  • Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, Cross JR, Jung E, Thompson CB, Jones RG. et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood. 2010;115(23):4742–4749. doi:10.1182/blood-2009-10-249540.
  • Guak H, Al Habyan S, Ma EH, Aldossary H, Al-Masri M, Won SY, Ying T, Fixman ED, Jones RG, McCaffrey LM. et al. Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration. Nat Commun. 2018;9(1):2463. doi:10.1038/s41467-018-04804-6.
  • Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 1999;5(11):1249–1255. doi:10.1038/15200.
  • Morrison VL, MacPherson M, Savinko T, Lek HS, Prescott A, Fagerholm SC. The β2 integrin–kindlin-3 interaction is essential for T-cell homing but dispensable for T-cell activation in vivo. Blood. 2013;122(8):1428–1436. doi:10.1182/BLOOD-2013-02-484998.
  • Uetz-von Allmen E, Samson GPB, Purvanov V, Maeda T, Legler DF. CAL-1 as cellular model system to study CCR7-guided human dendritic cell migration. Front Immunol. 2021;12:702453. doi:10.3389/fimmu.2021.702453.