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      KCI등재 SCOPUS SCIE

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

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      https://www.riss.kr/link?id=A106096699

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      다국어 초록 (Multilingual Abstract)

      CD4 T cells differentiate into RORγt/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 na?ve 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 na?ve 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.
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      CD4 T cells differentiate into RORγt/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 na?ve pre...

      CD4 T cells differentiate into RORγt/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 na?ve 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 na?ve 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.

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      참고문헌 (Reference)

      1 Aujla, S. J., "Th17 cells and mucosal host defense" 19 : 377-382, 2007

      2 Atarashi, K., "Th17 cell induction by adhesion of microbes to intestinal epithelial cells" 163 : 367-380, 2015

      3 Yang, X. O., "T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma" 28 : 29-39, 2008

      4 Goto, Y., "Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation" 40 : 594-607, 2014

      5 Maeda, Y., "Role of gut microbiota in rheumatoid arthritis" 6 : 60-, 2017

      6 Maynard, C. L., "Reciprocal interactions of the intestinal microbiota and immune system" 489 : 231-241, 2012

      7 Keerthivasan, S., "Notch signaling regulates mouse and human Th17differentiation" 187 : 692-701, 2011

      8 Klaasen, H. L., "Mono-association of mice with noncultivable, intestinal, segmented, filamentous bacteria" 156 : 148-151, 1991

      9 Sanchez-Freire, V., "Microfluidic single-cell real-time PCR for comparative analysis of gene expression patterns" 7 : 829-838, 2012

      10 Feng, T., "Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis" 207 : 1321-1332, 2010

      1 Aujla, S. J., "Th17 cells and mucosal host defense" 19 : 377-382, 2007

      2 Atarashi, K., "Th17 cell induction by adhesion of microbes to intestinal epithelial cells" 163 : 367-380, 2015

      3 Yang, X. O., "T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma" 28 : 29-39, 2008

      4 Goto, Y., "Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation" 40 : 594-607, 2014

      5 Maeda, Y., "Role of gut microbiota in rheumatoid arthritis" 6 : 60-, 2017

      6 Maynard, C. L., "Reciprocal interactions of the intestinal microbiota and immune system" 489 : 231-241, 2012

      7 Keerthivasan, S., "Notch signaling regulates mouse and human Th17differentiation" 187 : 692-701, 2011

      8 Klaasen, H. L., "Mono-association of mice with noncultivable, intestinal, segmented, filamentous bacteria" 156 : 148-151, 1991

      9 Sanchez-Freire, V., "Microfluidic single-cell real-time PCR for comparative analysis of gene expression patterns" 7 : 829-838, 2012

      10 Feng, T., "Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis" 207 : 1321-1332, 2010

      11 Kawabe, T., "Memoryphenotype CD4(+) T cells spontaneously generated under steadystate conditions exert innate TH1-like effector function" 2 : eaam9304-, 2017

      12 Geuking, M. B., "Intestinal bacterial colonization induces mutualistic regulatory T cell responses" 34 : 794-806, 2011

      13 Powrie, F., "Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells" 1 : 553-562, 1994

      14 Ivanov, II, Atarashi, K., "Induction of intestinal Th17 cells by segmented filamentous bacteria" 139 : 485-498, 2009

      15 Atarashi, K., "Induction of colonic regulatory T cells by indigenous Clostridium species" 331 : 337-341, 2011

      16 Round, J. L., "Inducible Foxp3+regulatory T-cell development by a commensal bacterium of the intestinal microbiota" 107 : 12204-12209, 2010

      17 Macdonald, T. T., "Immunity, inflammation, and allergy in the gut" 307 : 1920-1925, 2005

      18 Martin, C. E., "Homeostatic proliferation of mature T cells" 979 : 81-106, 2013

      19 Lee, Y. K., "Has the microbiota played a critical role in the evolution of the adaptive immune system?" 330 : 1768-1773, 2010

      20 Wu, H. J., "Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells" 32 : 815-827, 2010

      21 Teng, F., "Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer's patch T follicular helper cells" 44 : 875-888, 2016

      22 Benson, A., "Gut commensal bacteria direct a protective immune response against Toxoplasma gondii" 6 : 187-196, 2009

      23 Yang, Y., "Focused specificity of intestinal TH17 cells towards commensal bacterial antigens" 510 : 152-156, 2014

      24 Hirota, K., "Fate mapping of IL-17-producing T cells in inflammatory responses" 12 : 255-263, 2011

      25 Basdeo, S. A., "Ex-Th17(nonclassical Th1)cells are functionally distinct from classical Th1 and Th17 cells and are not constrained by regulatory T cells" 198 : 2249-2259, 2017

      26 Murphy, K. M., "Effector T cell plasticity : flexibility in the face of changing circumstances" 11 : 674-680, 2010

      27 Kelso, A., "Educating T cells : early events in the differentiation and commitment of cytokine-producing CD4+ and CD8+ T cells" 21 : 231-248, 1999

      28 윤병하, "Dynamic Transcriptome, DNA Methylome, and DNA Hydroxymethylome Networks During T-Cell Lineage Commitment" 한국분자세포생물학회 41 (41): 953-963, 2018

      29 Umesaki, Y., "Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system" 67 : 3504-3511, 1999

      30 Kim, K. S., "Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine" 351 : 858-863, 2016

      31 LeBlanc, J. G., "Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria" 16 : 79-, 2017

      32 Lodes, M. J., "Bacterial flagellin is a dominant antigen in Crohn disease" 113 : 1296-1306, 2004

      33 Sano, T., "An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses" 163 : 381-393, 2015

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2012-11-07 학술지명변경 한글명 : 분자와 세포 -> Molecules and Cells KCI등재
      2008-01-01 평가 SCI 등재 (등재유지) KCI등재
      2006-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2004-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2001-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      1998-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 2.77 0.19 1.85
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      1.37 1.11 0.379 0.03
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