PMID- 20304952 OWN - NLM STAT- MEDLINE DCOM- 20101215 LR - 20240511 IS - 1525-2191 (Electronic) IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 176 IP - 5 DP - 2010 May TI - Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. PG - 2367-77 LID - 10.2353/ajpath.2010.090723 [doi] AB - In the adult intestine, luminal microbiota induce cryptopatches to transform into isolated lymphoid follicles (ILFs), which subsequently act as sites for the generation of IgA responses. The events leading to this conversion are incompletely understood. Dendritic cells (DCs) are components of cryptopatches (CPs) and ILFs and were therefore evaluated in this process. We observed that the adult murine intestine contains clusters of DCs restricted to the CP/ILF continuum. A numerical and cell associative hierarchy in the adult intestine and a chronologic hierarchy in the neonatal intestine demonstrated that these clusters form after the coalescence of CD90+ cells to form CPs and before the influx of B220+ B lymphocytes to form ILFs. Cluster formation was dependent on lymphotoxin and the lymphotoxin beta receptor and independent of lymphocytes. The ILF DC population was distinguished from that of the lamina propria by the absence of CD4+CD11c+ cells and an increased proportion of CD11c+B220+ cells. The formation of clusters was not limited by DC numbers but was induced by luminal microbiota. Moreover, in the absence of the chemokine CXCL13, CP transformation into ILF was arrested. Furthermore, ILF DCs express CXCL13, and depletion of DCs resulted in regression of ILFs and disorganization of CPs. These results reveal DC participation in ILF transformation and maintenance and suggest that in part this may be due to CXCL13 production by these cells. FAU - McDonald, Keely G AU - McDonald KG AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - McDonough, Jacquelyn S AU - McDonough JS FAU - Dieckgraefe, Brian K AU - Dieckgraefe BK FAU - Newberry, Rodney D AU - Newberry RD LA - eng GR - R01 DK064798/DK/NIDDK NIH HHS/United States GR - P30 CA91842/CA/NCI NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - AG028309/AG/NIA NIH HHS/United States GR - P30 DK052574/DK/NIDDK NIH HHS/United States GR - R01 DK064798-07/DK/NIDDK NIH HHS/United States GR - R21 AG028309/AG/NIA NIH HHS/United States GR - DK64798/DK/NIDDK NIH HHS/United States GR - P30-DK52574/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100319 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Chemokine CXCL13) RN - 0 (Cxcl13 protein, mouse) RN - 0 (Thy-1 Antigens) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Animals MH - B-Lymphocytes/cytology MH - Chemokine CXCL13/*metabolism MH - Dendritic Cells/*cytology MH - Flow Cytometry/methods MH - *Gene Expression Regulation MH - Immune System MH - Intestine, Small/*metabolism MH - Leukocyte Common Antigens/metabolism MH - Lymphocytes/cytology MH - Lymphoid Tissue/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mucous Membrane/pathology MH - Thy-1 Antigens/biosynthesis PMC - PMC2861101 EDAT- 2010/03/23 06:00 MHDA- 2010/12/16 06:00 PMCR- 2011/05/01 CRDT- 2010/03/23 06:00 PHST- 2010/03/23 06:00 [entrez] PHST- 2010/03/23 06:00 [pubmed] PHST- 2010/12/16 06:00 [medline] PHST- 2011/05/01 00:00 [pmc-release] AID - S0002-9440(10)60032-6 [pii] AID - 10.2353/ajpath.2010.090723 [doi] PST - ppublish SO - Am J Pathol. 2010 May;176(5):2367-77. doi: 10.2353/ajpath.2010.090723. Epub 2010 Mar 19.