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A Stromal Cell Niche Sustains ILC2-Mediated Type-2 Conditioning in Adipose Tissue

ABSTRACT: Group-2 innate lymphoid cells (ILC2), type-2 cytokines and eosinophils, have all been implicated in sustaining adipose tissue homeostasis. However, the interplay between the stroma and adipose-resident immune cells is less well understood. We identify that white adipose tissue-resident multipotent stromal cells (WAT-MSCs) can act as a reservoir for IL-33, especially after cell stress, but also provide additional signals for sustaining ILC2. Indeed, we demonstrate that WAT-MSCs also support ICAM-1-mediated proliferation and activation of LFA-1-expressing ILC2s. Consequently, ILC2-derived IL-4 and IL-13 feed-back to induce eotaxin secretion from WAT-MSCs supporting eosinophil recruitment. Thus, MSCs provide a niche for multifaceted dialogue with ILC2 to sustain a type-2 immune environment in WAT.

ORGANISM(S): Mus musculus

PROVIDER: GSE132738 | GEO | 2019/06/24

REPOSITORIES: GEO

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Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-M-NM-1, MCP-1, RANTES, and IL-1M-NM-1 is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC. The microRNA expression of migratory subpopulations were compared to parental populations of MSCs.

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A Stromal Cell Niche Sustains ILC2-Mediated Type-2 Conditioning in Adipose Tissue

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