CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3+ T Cells

Cell Reports

Volumn 14, Issue 5, 2016, Pages 1041-1048

  Cowan, Jennifer E ^a,b   McCarthy, Nicholas I ^a   Anderson, Graham ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CCR6; CHEMOKINE RECEPTOR CCR7; GREEN FLUORESCENT PROTEIN; INTERLEUKIN 2 RECEPTOR ALPHA; RAG2 PROTEIN; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EMBRYO; LYMPHOCYTE COUNT; LYMPHOCYTE HOMING; LYMPHOCYTE MIGRATION; LYMPHOCYTE RECIRCULATION; LYMPHOCYTE SUBPOPULATION; LYMPHOCYTOPOIESIS; MOUSE; NONHUMAN; PRE T LYMPHOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; THYMOCYTE; THYMUS; ANIMAL; C57BL MOUSE; CELL DIFFERENTIATION; CELL MOTION; CYTOLOGY; METABOLISM; TRANSGENIC MOUSE;

ANIMALS; CELL DIFFERENTIATION; CELL MOVEMENT; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; MICE, INBRED C57BL; MICE, TRANSGENIC; RECEPTORS, CCR6; RECEPTORS, CCR7; T-LYMPHOCYTES, REGULATORY; THYMUS GLAND;

EID: 84958012871     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.01.003     Document Type: Article

References (32)

1. Berzins S.P., Boyd R.L., Miller J.F. The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. J. Exp. Med. 1998, 187:1839-1848.
2. Boehm T., Scheu S., Pfeffer K., Bleul C.C. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. J. Exp. Med. 2003, 198:757-769.
3. Boursalian T.E., Golob J., Soper D.M., Cooper C.J., Fink P.J. Continued maturation of thymic emigrants in the periphery. Nat. Immunol. 2004, 5:418-425.
4. Campbell D.J. Control of regulatory T cell migration, function, and homeostasis. J. Immunol. 2015, 195:2507-2513.
5. Coquet J.M., Ribot J.C., Babała N., Middendorp S., van der Horst G., Xiao Y., Neves J.F., Fonseca-Pereira D., Jacobs H., Pennington D.J., et al. Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway. J. Exp. Med. 2013, 210:715-728.
6. Cowan J.E., Parnell S.M., Nakamura K., Caamano J.H., Lane P.J., Jenkinson E.J., Jenkinson W.E., Anderson G. The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J. Exp. Med. 2013, 210:675-681.
7. Cowan J.E., McCarthy N.I., Parnell S.M., White A.J., Bacon A., Serge A., Irla M., Lane P.J., Jenkinson E.J., Jenkinson W.E., Anderson G. Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus. J. Immunol. 2014, 193:1204-1212.
8. Davalos-Misslitz A.C., Worbs T., Willenzon S., Bernhardt G., Förster R. Impaired responsiveness to T-cell receptor stimulation and defective negative selection of thymocytes in CCR7-deficient mice. Blood 2007, 110:4351-4359.
9. Hale J.S., Fink P.J. Back to the thymus: peripheral T cells come home. Immunol. Cell Biol. 2009, 87:58-64.
10. Hauri-Hohl M., Zuklys S., Holländer G.A., Ziegler S.F. A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla. Nat. Immunol. 2014, 15:554-561.
11. Koble C., Kyewski B. The thymic medulla: a unique microenvironment for intercellular self-antigen transfer. J. Exp. Med. 2009, 206:1505-1513.
12. Kurobe H., Liu C., Ueno T., Saito F., Ohigashi I., Seach N., Arakaki R., Hayashi Y., Kitagawa T., Lipp M., et al. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Immunity 2006, 24:165-177.
13. Kwan J., Killeen N. CCR7 directs the migration of thymocytes into the thymic medulla. J. Immunol. 2004, 172:3999-4007.
14. Lio C.W., Hsieh C.S. A two-step process for thymic regulatory T cell development. Immunity 2008, 28:100-111.
15. Liston A., Nutsch K.M., Farr A.G., Lund J.M., Rasmussen J.P., Koni P.A., Rudensky A.Y. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc. Natl. Acad. Sci. USA 2008, 105:11903-11908.
16. Liu C., Wang H.C., Yu S., Jin R., Tang H., Liu Y.F., Ge Q., Sun X.H., Zhang Y. Id1 expression promotes T regulatory cell differentiation by facilitating TCR costimulation. J. Immunol. 2014, 193:663-672.
17. McCarthy N.I., Cowan J.E., Nakamura K., Bacon A., Baik S., White A.J., Parnell S.M., Jenkinson E.J., Jenkinson W.E., Anderson G. Osteoprotegerin-mediated homeostasis of rank+ thymic epithelial cells does not limit Foxp3+ regulatory T cell development. J. Immunol. 2015, 195:2675-2682.
18. McCaughtry T.M., Wilken M.S., Hogquist K.A. Thymic emigration revisited. J. Exp. Med. 2007, 204:2513-2520.
19. Murata S., Sasaki K., Kishimoto T., Niwa S., Hayashi H., Takahama Y., Tanaka K. Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 2007, 316:1349-1353.
20. Nitta T., Nitta S., Lei Y., Lipp M., Takahama Y. CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens. Proc. Natl. Acad. Sci. USA 2009, 106:17129-17133.
21. Ohigashi I., Zuklys S., Sakata M., Mayer C.E., Hamazaki Y., Minato N., Hollander G.A., Takahama Y. Adult thymic medullary epithelium is maintained and regenerated by lineage-restricted cells rather than bipotent progenitors. Cell Rep. 2015, 13:1432-1443.
22. Pahuja A., Maki R.A., Hevezi P.A., Chen A., Verge G.M., Lechner S.M., Roth R.B., Zlotnik A., Alleva D.G. Experimental autoimmune encephalomyelitis develops in CC chemokine receptor 7-deficient mice with altered T-cell responses. Scand. J. Immunol. 2006, 64:361-369.
23. Schneider M.A., Meingassner J.G., Lipp M., Moore H.D., Rot A. CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells. J. Exp. Med. 2007, 204:735-745.
24. Tai X., Erman B., Alag A., Mu J., Kimura M., Katz G., Guinter T., McCaughtry T., Etzensperger R., Feigenbaum L., et al. Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals. Immunity 2013, 38:1116-1128.
25. Takaba H., Morishita Y., Tomofuji Y., Danks L., Nitta T., Komatsu N., Kodama T., Takayanagi H. Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance. Cell 2015, 163:975-987.
26. Thiault N., Darrigues J., Adoue V., Gros M., Binet B., Perals C., Leobon B., Fazilleau N., Joffre O.P., Robey E.A., et al. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat. Immunol. 2015, 16:628-634.
27. Ueno T., Hara K., Willis M.S., Malin M.A., Höpken U.E., Gray D.H., Matsushima K., Lipp M., Springer T.A., Boyd R.L., et al. Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Immunity 2002, 16:205-218.
28. Ueno T., Saito F., Gray D.H., Kuse S., Hieshima K., Nakano H., Kakiuchi T., Lipp M., Boyd R.L., Takahama Y. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. J. Exp. Med. 2004, 200:493-505.
29. Wan Y.Y., Flavell R.A. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc. Natl. Acad. Sci. USA 2005, 102:5126-5131.
30. Weist B.M., Kurd N., Boussier J., Chan S.W., Robey E.A. Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition. Nat. Immunol. 2015, 16:635-641.
31. Yang E., Zou T., Leichner T.M., Zhang S.L., Kambayashi T. Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus. Eur. J. Immunol. 2014, 44:2712-2720.
32. Yu W., Nagaoka H., Jankovic M., Misulovin Z., Suh H., Rolink A., Melchers F., Meffre E., Nussenzweig M.C. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization. Nature 1999, 400:682-687.