Colonic patch and colonic SILT development are independent and differentially regulated events

Mucosal Immunol. 2013 May;6(3):511-21. doi: 10.1038/mi.2012.90. Epub 2012 Sep 19.

Abstract

Intestinal lymphoid tissues have to simultaneously ensure protection against pathogens and tolerance toward commensals. Despite such vital functions, their development in the colon is poorly understood. Here, we show that the two distinct lymphoid tissues of the colon-colonic patches and colonic solitary intestinal lymphoid tissues (SILTs)-can easily be distinguished based on anatomical location, developmental timeframe, and cellular organization. Furthermore, whereas colonic patch development depended on CXCL13-mediated lymphoid tissue inducer (LTi) cell clustering followed by LTα-mediated consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6, or CXCR3. Subsequent dendritic cell recruitment to and gp38(+)VCAM-1(+) lymphoid stromal cell differentiation within SILTs required LTα; B-cell recruitment and follicular dendritic cell differentiation depended on MyD88-mediated signaling, but not the microflora. In conclusion, our data demonstrate that different mechanisms, mediated mainly by programmed stimuli, induce the formation of distinct colonic lymphoid tissues, therefore suggesting that these tissues may have different functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL13 / genetics
  • Chemokine CXCL13 / metabolism
  • Colon / anatomy & histology
  • Colon / immunology*
  • Dendritic Cells / immunology*
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / growth & development
  • Lymphoid Tissue / immunology*
  • Lymphotoxin-alpha / immunology
  • Lymphotoxin-alpha / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • Receptors, CXCR3 / metabolism
  • Signal Transduction
  • Stromal Cells / immunology*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • CCR6 protein, mouse
  • Chemokine CXCL13
  • Cxcr3 protein, mouse
  • Gp38 protein, mouse
  • Lymphotoxin-alpha
  • Membrane Glycoproteins
  • Myeloid Differentiation Factor 88
  • Receptors, CCR6
  • Receptors, CXCR3
  • Vascular Cell Adhesion Molecule-1