title: Crosstalk Between T Lymphocytes and Lung Fibroblasts: Generation of a Hyaluronan-Enriched Extracellular Matrix Adhesive for Monocytes.
abstract: In immunity and inflammation, T cells are often associated with stromal mesenchymal cells such as fibroblasts. Hyaluronan and proteins that associate with hyaluronan such as versican and tumor necrosis factor-inducible gene-6 (TSG-6) are extracellular matrix (ECM) components that promote leukocyte adhesion, accumulation, and activation. However, the factors responsible for producing this specialized ECM and its impact on inflammatory events are not well understood. In this study, we explored the role of T cells in stimulating lung fibroblasts to produce an ECM that impacts monocyte adhesion. We found that CD3/CD28-activated human CD4+ T cells when co-cultured with human lung fibroblasts stimulated the expression of mRNA for hyaluronan synthase 2 (HAS2) and decreased the expression of hyaluronidase 2 (HYAL2). This led to an increase in the deposition of hyaluronan that formed cable-like structures within the ECM. Co-culturing activated T cells with fibroblasts also led to increased expression and accumulation of TSG-6. Surprisingly, addition of activated CD4+ T cells to the fibroblasts reduced the expression of mRNA for versican, and increased the expression of enzymes that degrade versican, such as ADAMTS4 and ADAMTS9 (a disintegrin and metalloproteinase with a thrombospondin type-1 motif) leading to a decrease in versican in the ECM of the co-cultures. Furthermore, addition of human monocytes to these co-cultures resulted in elevated monocyte adhesion to the cable-like structures in the ECM when compared to controls. These results illustrate the importance of crosstalk between T cells and fibroblasts in promoting the generation of a matrix that is adhesive for monocytes. J. Cell. Biochem. 118: 2118-2130, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Léa
authors.initials: L
authors.lastname: Gaucherand
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Falk
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Evanko
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Gail
authors.initials: G
authors.lastname: Workman
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Chan
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Thomas N
authors.identifier: 0000-0002-2794-4197
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000071121:ADAMTS4 Protein / Q000235:genetics / Q000276:immunology; D000071119:ADAMTS9 Protein / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000276:immunology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D014453:Glucuronosyltransferase / Q000235:genetics / Q000276:immunology; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000276:immunology; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D053675:Versicans / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C072273:TNFAIP6 protein, human; D053675:Versicans; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human; D000071121:ADAMTS4 Protein
keywords:  INFLAMMATION; ADAMTS; CO-CULTURE; EXTRACELLULAR MATRIX; FIBROBLASTS; HYALURONAN; LEUKOCYTES; LYMPHOCYTES; MONOCYTES; TSG-6; VERSICAN