IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells

English version České info

In order to mount a protective response against numerous and enormously diverse microbial pathogens, T cells are able to differentiate into functionally distinct helper T (Th) subsets. To control different types of T cell immunity in a given inflammatory setting, regulatory T (Treg) cells have emerged as a dedicated immune population crucial for the negative regulation of immune responses. Here, we show that IL-27 derived from IFNγ responding dendritic cells (DCs) is crucial to drive the differentiation of a specialized Th1-Treg cell subset to limit IFNγ-mediated Th1 inflammation in a parasitic infection setting. The new cellular and molecular insights of our study not only challenge the current idea of Th1-Treg cell differentiation but also provide evidence of a more complex immune response and regulation scenario highlighted by the Treg cell-extrinsic and DC-intrinsic role of IFNγ signaling in Treg cell-mediated regulation of Th1 immunity particularly during Toxoplasma gondii infection.

Vyšlo v časopise: IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004635
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004635

Souhrn

Zdroje

1. Nakayamada S, Takahashi H, Kanno Y, O'Shea JJ (2012) Helper T cell diversity and plasticity. Curr Opin Immunol 24: 297–302. doi: 10.1016/j.coi.2012.01.014 22341735

2. Josefowicz SZ, Lu LF, Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30: 531–564. doi: 10.1146/annurev.immunol.25.022106.141623 22224781

3. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6: 1142–1151. 16227984

4. Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, et al. (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445: 771–775. 17220874

5. Wan YY, Flavell RA (2007) Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445: 766–770. 17220876

6. Campbell DJ, Koch MA (2011) Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat Rev Immunol 11: 119–130. doi: 10.1038/nri2916 21267013

7. Koch MA, Tucker-Heard G, Perdue NR, Killebrew JR, Urdahl KB, et al. (2009) The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol 10: 595–602. doi: 10.1038/ni.1731 19412181

8. Zheng Y, Chaudhry A, Kas A, deRoos P, Kim JM, et al. (2009) Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458: 351–356. doi: 10.1038/nature07674 19182775

9. Chaudhry A, Rudra D, Treuting P, Samstein RM, Liang Y, et al. (2009) CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326: 986–991. doi: 10.1126/science.1172702 19797626

10. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, et al. (2011) Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 17: 975–982. doi: 10.1038/nm.2425 21785433

11. Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, et al. (2011) Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med 17: 983–988. doi: 10.1038/nm.2426 21785430

12. Koch MA, Thomas KR, Perdue NR, Smigiel KS, Srivastava S, et al. (2012) T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor beta2. Immunity 37: 501–510. doi: 10.1016/j.immuni.2012.05.031 22960221

13. Hall AO, Beiting DP, Tato C, John B, Oldenhove G, et al. (2012) The cytokines interleukin 27 and interferon-gamma promote distinct Treg cell populations required to limit infection-induced pathology. Immunity 37: 511–523. doi: 10.1016/j.immuni.2012.06.014 22981537

14. Hemmi S, Bohni R, Stark G, Di Marco F, Aguet M (1994) A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor in human cells. Cell 76: 803–810. 8124717

15. Yamazaki S, Morita A (2013) Dendritic cells in the periphery control antigen-specific natural and induced regulatory T cells. Front Immunol 4: 151. doi: 10.3389/fimmu.2013.00151 23801989

16. Soroosh P, Doherty TA, Duan W, Mehta AK, Choi H, et al. (2013) Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance. J Exp Med 210: 775–788. doi: 10.1084/jem.20121849 23547101

17. Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-gamma. Annu Rev Immunol 15: 749–795. 9143706

18. Lee SH, Carrero JA, Uppaluri R, White JM, Archambault JM, et al. (2013) Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFN-gamma receptor subunit 1 (IFNGR1). J Immunol 191: 4223–4234. doi: 10.4049/jimmunol.1300910 24048899

19. Oldenhove G, Bouladoux N, Wohlfert EA, Hall JA, Chou D, et al. (2009) Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31: 772–786. doi: 10.1016/j.immuni.2009.10.001 19896394

20. Liesenfeld O, Kosek J, Remington JS, Suzuki Y (1996) Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 184: 597–607. 8760813

21. Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, et al. (2010) Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142: 914–929. doi: 10.1016/j.cell.2010.08.012 20850013

22. Chaudhry A, Rudensky AY (2013) Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest 123: 939–944. doi: 10.1172/JCI57175 23454755

23. He T, Tang C, Xu S, Moyana T, Xiang J (2007) Interferon gamma stimulates cellular maturation of dendritic cell line DC2.4 leading to induction of efficient cytotoxic T cell responses and antitumor immunity. Cell Mol Immunol 4: 105–111. 17484804

24. Lemoine R, Velge-Roussel F, Herr F, Felix R, Nivet H, et al. (2010) Interferon gamma licensing of human dendritic cells in T-helper-independent CD8+ alloimmunity. Blood 116: 3089–3098. doi: 10.1182/blood-2010-02-268623 20644110

25. Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, et al. (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8: 1380–1389. 17994022

26. Fitzgerald DC, Zhang GX, El-Behi M, Fonseca-Kelly Z, Li H, et al. (2007) Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 8: 1372–1379. 17994023

27. Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, et al. (2007) Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8: 1363–1371. 17994025

28. Zhang S, Liang R, Luo W, Liu C, Wu X, et al. (2013) High susceptibility to liver injury in IL-27 p28 conditional knockout mice involves intrinsic interferon-gamma dysregulation of CD4+ T cells. Hepatology 57: 1620–1631. doi: 10.1002/hep.26166 23175475

29. Steinman RM (2003) Some interfaces of dendritic cell biology. APMIS 111: 675–697. 12974772

30. de Jong EC, Smits HH, Kapsenberg ML (2005) Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol 26: 289–307. 15609003

31. Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21: 685–711. 12615891

32. Findlay EG, Greig R, Stumhofer JS, Hafalla JC, de Souza JB, et al. (2010) Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection. J Immunol 185: 2482–2492. doi: 10.4049/jimmunol.0904019 20631310

33. Villegas-Mendez A, de Souza JB, Lavelle SW, Gwyer Findlay E, Shaw TN, et al. (2013) IL-27 receptor signalling restricts the formation of pathogenic, terminally differentiated Th1 cells during malaria infection by repressing IL-12 dependent signals. PLoS Pathog 9: e1003293. doi: 10.1371/journal.ppat.1003293 23593003

34. Kernbauer E, Maier V, Stoiber D, Strobl B, Schneckenleithner C, et al. (2012) Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection. PLoS Pathog 8: e1002763. doi: 10.1371/journal.ppat.1002763 22719255

35. Hotson AN, Hardy JW, Hale MB, Contag CH, Nolan GP (2009) The T cell STAT signaling network is reprogrammed within hours of bacteremia via secondary signals. J Immunol 182: 7558–7568. doi: 10.4049/jimmunol.0803666 19494279

36. Groom JR, Richmond J, Murooka TT, Sorensen EW, Sung JH, et al. (2012) CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 37: 1091–1103. doi: 10.1016/j.immuni.2012.08.016 23123063

37. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castell L, et al. (2008) IL-10 produced by regulatory T cells contributes to their suppressor function by limiting inflammation at environmental interfaces. Immunity 28: 546–558. doi: 10.1016/j.immuni.2008.02.017 18387831

38. Pszenny V, Davis PH, Zhou XW, Hunter CA, Carruthers VB, et al. (2012) Targeted disruption of Toxoplasma gondii serine protease inhibitor 1 increases bradyzoite cyst formation in vitro and parasite tissue burden in mice. Infect Immun 80: 1156–1165. doi: 10.1128/IAI.06167-11 22202120

39. Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, et al. (2009) Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30: 80–91. doi: 10.1016/j.immuni.2008.11.010 19144316