Browse > Article
http://dx.doi.org/10.14348/molcells.2018.0424

Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine  

Yi, Jaeu (Academy of Immunology and Microbiology, Institute for Basic Science)
Jung, Jisun (Academy of Immunology and Microbiology, Institute for Basic Science)
Han, Daehee (Academy of Immunology and Microbiology, Institute for Basic Science)
Surh, Charles D. (Academy of Immunology and Microbiology, Institute for Basic Science)
Lee, You Jeong (Academy of Immunology and Microbiology, Institute for Basic Science)
Publication Information
Molecules and Cells / v.42, no.3, 2019 , pp. 228-236 More about this Journal
Abstract
CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.
Keywords
antigen-specific CD4 T cells; germ-free mice; segmented filamentous bacteria; single cell RT-PCR; small intestine;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Teng, F., Klinger, C.N., Felix, K.M., Bradley, C.P., Wu, E., Tran, N.L., Umesaki, Y., and Wu, H.J. (2016). Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer's patch T follicular helper cells. Immunity 44, 875-888.   DOI
2 Umesaki, Y., Setoyama, H., Matsumoto, S., Imaoka, A., and Itoh, K. (1999). Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect. Immun. 67, 3504-3511.   DOI
3 Wu, H.J., Ivanov, II, Darce, J., Hattori, K., Shima, T., Umesaki, Y., Littman, D.R., Benoist, C., and Mathis, D. (2010). Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815-827.   DOI
4 Yang, X.O., Pappu, B.P., Nurieva, R., Akimzhanov, A., Kang, H.S., Chung, Y., Ma, L., Shah, B., Panopoulos, A.D., Schluns, K.S., et al. (2008). T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28, 29-39.   DOI
5 Yang, Y., Torchinsky, M.B., Gobert, M., Xiong, H., Xu, M., Linehan, J.L., Alonzo, F., Ng, C., Chen, A., Lin, X., et al. (2014). Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152-156.   DOI
6 Yoon, B.H., Kim, M., Kim, M.H., Kim, H.J., Kim, J.H., Kim, J.H., Kim, J., Kim, Y.S., Lee, D., Kang, S.J., et al. (2018). Dynamic transcriptome, DNA methylome, and DNA hydroxymethylome networks during T-cell lineage commitment. Mol. Cells 41, 953-963.   DOI
7 Hirota, K., Duarte, J.H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D.J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011). Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol. 12, 255-263.   DOI
8 Ivanov, II, Atarashi, K., Manel, N., Brodie, E.L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K.C., Santee, C.A., Lynch, S.V., et al. (2009). Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485-498.   DOI
9 Kawabe, T., Jankovic, D., Kawabe, S., Huang, Y., Lee, P.H., Yamane, H., Zhu, J., Sher, A., Germain, R.N., and Paul, W.E. (2017). Memory-phenotype CD4(+) T cells spontaneously generated under steady-state conditions exert innate TH1-like effector function. Sci. Immunol. 2, eaam9304.   DOI
10 Keerthivasan, S., Suleiman, R., Lawlor, R., Roderick, J., Bates, T., Minter, L., Anguita, J., Juncadella, I., Nickoloff, B.J., Le Poole, I.C., et al. (2011). Notch signaling regulates mouse and human Th17 differentiation. J. Immunol. 187, 692-701.   DOI
11 Kelso, A. (1999). Educating T cells: early events in the differentiation and commitment of cytokine-producing CD4+ and CD8+ T cells. Springer Semin. Immunopathol. 21, 231-248.   DOI
12 Aujla, S.J., Dubin, P.J., and Kolls, J.K. (2007). Th17 cells and mucosal host defense. Semin Immunol 19, 377-382.   DOI
13 Kim, K.S., Hong, S.W., Han, D., Yi, J., Jung, J., Yang, B.G., Lee, J.Y., Lee, M., and Surh, C.D. (2016). Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351, 858-863.   DOI
14 Klaasen, H.L., Koopman, J.P., Van den Brink, M.E., Van Wezel, H.P., and Beynen, A.C. (1991). Mono-association of mice with non-cultivable, intestinal, segmented, filamentous bacteria. Arch. Microbiol. 156, 148-151.   DOI
15 LeBlanc, J.G., Chain, F., Martin, R., Bermudez-Humaran, L.G., Courau, S., and Langella, P. (2017). Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb. Cell Fact. 16, 79.   DOI
16 Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., et al. (2015). Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163, 367-380.   DOI
17 Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011). Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337-341.   DOI
18 Basdeo, S.A., Cluxton, D., Sulaimani, J., Moran, B., Canavan, M., Orr, C., Veale, D.J., Fearon, U., and Fletcher, J.M. (2017). Ex-Th17 (nonclassical Th1) cells are functionally distinct from classical Th1 and Th17 cells and are not constrained by regulatory T cells. J. Immunol. 198, 2249-2259.   DOI
19 Benson, A., Pifer, R., Behrendt, C.L., Hooper, L.V., and Yarovinsky, F. (2009). Gut commensal bacteria direct a protective immune response against Toxoplasma gondii. Cell Host Microbe 6, 187-196.   DOI
20 Feng, T., Wang, L., Schoeb, T.R., Elson, C.O., and Cong, Y. (2010). Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J. Exp. Med. 207, 1321-1332.   DOI
21 Geuking, M.B., Cahenzli, J., Lawson, M.A., Ng, D.C., Slack, E., Hapfelmeier, S., McCoy, K.D., and Macpherson, A.J. (2011). Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34, 794-806.   DOI
22 Goto, Y., Panea, C., Nakato, G., Cebula, A., Lee, C., Diez, M.G., Laufer, T.M., Ignatowicz, L., and Ivanov, II (2014). Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 40, 594-607.   DOI
23 Maeda, Y., and Takeda, K. (2017). Role of gut microbiota in rheumatoid arthritis. J. Clin. Med. 6, 60.   DOI
24 Lee, Y.K., and Mazmanian, S.K. (2010). Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330, 1768-1773.   DOI
25 Lodes, M.J., Cong, Y., Elson, C.O., Mohamath, R., Landers, C.J., Targan, S.R., Fort, M., and Hershberg, R.M. (2004). Bacterial flagellin is a dominant antigen in Crohn disease. J. Clin. Invest. 113, 1296-1306.   DOI
26 Macdonald, T.T., and Monteleone, G. (2005). Immunity, inflammation, and allergy in the gut. Science 307, 1920-1925.   DOI
27 Powrie, F., Leach, M.W., Mauze, S., Menon, S., Caddle, L.B., and Coffman, R.L. (1994). Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1, 553-562.   DOI
28 Martin, C.E., Frimpong-Boateng, K., Spasova, D.S., Stone, J.C., and Surh, C.D. (2013). Homeostatic proliferation of mature T cells. Methods Mol. Biol. 979, 81-106.   DOI
29 Maynard, C.L., Elson, C.O., Hatton, R.D., and Weaver, C.T. (2012). Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231-241.   DOI
30 Murphy, K.M., and Stockinger, B. (2010). Effector T cell plasticity: flexibility in the face of changing circumstances. Nat. Immunol. 11, 674-680.   DOI
31 Round, J.L., and Mazmanian, S.K. (2010). Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. Sci. USA 107, 12204-12209.   DOI
32 Sanchez-Freire, V., Ebert, A.D., Kalisky, T., Quake, S.R., and Wu, J.C. (2012). Microfluidic single-cell real-time PCR for comparative analysis of gene expression patterns. Nat. Protoc. 7, 829-838.   DOI
33 Sano, T., Huang, W., Hall, J.A., Yang, Y., Chen, A., Gavzy, S.J., Lee, J.Y., Ziel, J.W., Miraldi, E.R., Domingos, A.I., et al. (2015). An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses. Cell 163, 381-393.   DOI