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Tracking of Follicular T Cell Dynamics During Immune Responses and Inflammation

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Chronic Inflammation

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Abstract

Follicular helper T (Tfh) cells are a subtype of helper T cells critical for antibody responses, particularly germinal centre (GC) responses in the lymphoid organs. Tfh cells can become memory Tfh cells, which play important roles in memory antibody responses. Memory Tfh cells, after exiting the lymphoid organs into the circulation, possibly induce memory responses in lymphoid organs distal from the vaccination site. Circulating memory Tfh cells may also contribute to ectopic GC responses in inflamed nonlymphoid organs. Tfh cells and memory Tfh cells seem to be also involved in the development of autoimmune diseases. Human blood memory Tfh cells have begun to be characterised in detail to understand their function in protective or pathological antibody responses. Mouse studies, especially those using live imaging techniques, have illustrated Tfh cell dynamics within the lymphoid organs and identified important molecules that regulate them. In addition, imaging studies using photoactivatable or photoconvertible fluorescent probes have started to reveal how Tfh cells exit the lymphoid organs to become circulating memory cells. In future studies, in order to investigate directly the involvement of circulating memory Tfh cells in memory responses and inflammatory diseases, it is important to develop new methods to genetically and/or optogenetically manipulate Tfh cells for longitudinal tracking of their cell fate.

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References

  • Allen CD, Okada T, Cyster JG (2007) Germinal-center organization and cellular dynamics. Immunity 27(2):190–202. doi:10.1016/j.immuni.2007.07.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bacchus W, Fussenegger M (2012) The use of light for engineered control and reprogramming of cellular functions. Curr Opin Biotechnol 23(5):695–702. doi:10.1016/j.copbio.2011.12.004

    Article  CAS  PubMed  Google Scholar 

  • Bubier JA, Sproule TJ, Foreman O, Spolski R, Shaffer DJ, Morse HC 3rd, Leonard WJ, Roopenian DC (2009) A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A 106(5):1518–1523. doi:10.1073/pnas.0807309106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crotty S, Johnston RJ, Schoenberger SP (2010) Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol 11(2):114–120, doi:ni.1837[pii]10.1038/ni.1837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cyster JG, Schwab SR (2012) Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs. Annu Rev Immunol 30:69–94. doi:10.1146/annurev-immunol-020711-075011

    Article  CAS  PubMed  Google Scholar 

  • Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ (2010) PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 11(6):535–542. doi:10.1038/ni.1877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green JA, Suzuki K, Cho B, Willison LD, Palmer D, Allen CD, Schmidt TH, Xu Y, Proia RL, Coughlin SR, Cyster JG (2011) The sphingosine 1-phosphate receptor S1P(2) maintains the homeostasis of germinal center B cells and promotes niche confinement. Nat Immunol 12(7):672–680. doi:10.1038/ni.2047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hale JS, Ahmed R (2015) Memory T follicular helper CD4 T cells. Front Immunol 6:16. doi:10.3389/fimmu.2015.00016

    Article  PubMed  PubMed Central  Google Scholar 

  • Ise W, Inoue T, McLachlan JB, Kometani K, Kubo M, Okada T, Kurosaki T (2014) Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells. Proc Natl Acad Sci U S A 111(32):11792–11797. doi:10.1073/pnas.1404671111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato LM, Kawamoto S, Maruya M, Fagarasan S (2014) The role of the adaptive immune system in regulation of gut microbiota. Immunol Rev 260(1):67–75. doi:10.1111/imr.12185

    Article  CAS  PubMed  Google Scholar 

  • Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL (2010) Rapid blue-light-mediated induction of protein interactions in living cells. Nat Methods 7(12):973–975. doi:10.1038/nmeth.1524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitano M, Moriyama S, Ando Y, Hikida M, Mori Y, Kurosaki T, Okada T (2011) Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity. Immunity 34(6):961–972. doi:10.1016/j.immuni.2011.03.025

    Article  CAS  PubMed  Google Scholar 

  • MacLennan IC, Gulbranson-Judge A, Toellner KM, Casamayor-Palleja M, Chan E, Sze DM, Luther SA, Orbea HA (1997) The changing preference of T and B cells for partners as T-dependent antibody responses develop. Immunol Rev 156:53–66

    Article  CAS  PubMed  Google Scholar 

  • Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13(1):133–140. doi:10.1038/nn.2467

    Article  CAS  PubMed  Google Scholar 

  • Moriyama S, Takahashi N, Green JA, Hori S, Kubo M, Cyster JG, Okada T (2014) Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers. J Exp Med 211(7):1297–1305. doi:10.1084/jem.20131666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173. doi:10.1146/annurev.iy.07.040189.001045

    Article  CAS  PubMed  Google Scholar 

  • Okada T, Moriyama S, Kitano M (2012) Differentiation of germinal center B cells and follicular helper T cells as viewed by tracking Bcl6 expression dynamics. Immunol Rev 247(1):120–132. doi:10.1111/j.1600-065X.2012.01120.x

    Article  PubMed  Google Scholar 

  • Pitzalis C, Jones GW, Bombardieri M, Jones SA (2014) Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat Rev Immunol 14(7):447–462. doi:10.1038/nri3700

    Article  CAS  PubMed  Google Scholar 

  • Pratama A, Ramiscal RR, Silva DG, Das SK, Athanasopoulos V, Fitch J, Botelho NK, Chang PP, Hu X, Hogan JJ, Mana P, Bernal D, Korner H, Yu D, Goodnow CC, Cook MC, Vinuesa CG (2013) Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Immunity 38(4):669–680. doi:10.1016/j.immuni.2013.01.011

    Article  CAS  PubMed  Google Scholar 

  • Schindler SE, McCall JG, Yan P, Hyrc KL, Li M, Tucker CL, Lee JM, Bruchas MR, Diamond MI (2015) Photo-activatable Cre recombinase regulates gene expression in vivo. Scientific Reports 5:13627. doi:10.1038/srep13627

    Article  PubMed  PubMed Central  Google Scholar 

  • Shinnakasu R, Inoue T, Kometani K, Moriyama S, Adachi Y, Nakayama M, Takahashi Y, Fukuyama H, Okada T, Kurosaki T (2016) Regulated selection of germinal-center cells into the memory B cell compartment. Nat Immunol [Epub ahead of print]. doi:10.1038/ni.3460

    Google Scholar 

  • Shulman Z, Gitlin AD, Targ S, Jankovic M, Pasqual G, Nussenzweig MC, Victora GD (2013) T follicular helper cell dynamics in germinal centers. Science 341(6146):673–677. doi:10.1126/science.1241680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suan D, Nguyen A, Moran I, Bourne K, Hermes JR, Arshi M, Hampton HR, Tomura M, Miwa Y, Kelleher AD, Kaplan W, Deenick EK, Tangye SG, Brink R, Chtanova T, Phan TG (2015) T follicular helper cells have distinct modes of migration and molecular signatures in naive and memory immune responses. Immunity 42(4):704–718. doi:10.1016/j.immuni.2015.03.002

    Article  CAS  PubMed  Google Scholar 

  • Taslimi A, Vrana JD, Chen D, Borinskaya S, Mayer BJ, Kennedy MJ, Tucker CL (2014) An optimized optogenetic clustering tool for probing protein interaction and function. Nat Commun 5:4925. doi:10.1038/ncomms5925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueno H, Banchereau J, Vinuesa CG (2015) Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol 16(2):142–152. doi:10.1038/ni.3054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Victora GD, Nussenzweig MC (2012) Germinal centers. Annu Rev Immunol 30:429–457. doi:10.1146/annurev-immunol-020711-075032

    Article  CAS  PubMed  Google Scholar 

  • Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, Hill KM, Yu D, Domaschenz H, Whittle B, Lambe T, Roberts IS, Copley RR, Bell JI, Cornall RJ, Goodnow CC (2005) A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435(7041):452–458. doi:10.1038/nature03555

    Article  CAS  PubMed  Google Scholar 

  • Vogel KU, Edelmann SL, Jeltsch KM, Bertossi A, Heger K, Heinz GA, Zoller J, Warth SC, Hoefig KP, Lohs C, Neff F, Kremmer E, Schick J, Repsilber D, Geerlof A, Blum H, Wurst W, Heikenwalder M, Schmidt-Supprian M, Heissmeyer V (2013) Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation. Immunity 38(4):655–668. doi:10.1016/j.immuni.2012.12.004

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Chen X, Yang Y (2012) Spatiotemporal control of gene expression by a light-switchable transgene system. Nat Methods 9(3):266–269. doi:10.1038/nmeth.1892

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan

    Takaharu Okada

  2. PRESTO, Japan Science and Technology Agency, Kawaguchi, 332-0012, Japan

    Takaharu Okada

  3. Graduate School of Medical Life Science, Yokohama City University, Yokohama, 230-0045, Japan

    Takaharu Okada

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  1. Takaharu Okada
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Correspondence to Takaharu Okada .

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Editors and Affiliations

  1. Interdisciplinary Program for Biomedical Sciences Institute for Academic Initiatives, Osaka University, Suita, Japan

    Masayuki Miyasaka

  2. Department of Immunobiology and Pharmacological Genetics Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Kiyoshi Takatsu

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Okada, T. (2016). Tracking of Follicular T Cell Dynamics During Immune Responses and Inflammation. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_13

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