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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.

SUBMITTER: Rana BMJ

PROVIDER: S-EPMC6719433 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue.

Rana Batika M J BMJ Jou Eric E Barlow Jillian L JL Rodriguez-Rodriguez Noe N Walker Jennifer A JA Knox Claire C Jolin Helen E HE Hardman Clare S CS Sivasubramaniam Meera M Szeto Aydan A Cohen E Suzanne ES Scott Ian C IC Sleeman Matthew A MA Chidomere Chiamaka I CI Cruz Migoni Sara S Caamano Jorge J Jorgensen Helle F HF Carobbio Stefania S Vidal-Puig Antonio A McKenzie Andrew N J ANJ

The Journal of experimental medicine 20190627 9

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- ...[more]

PMID: 31248899

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Project description:Osteoarthritis (OA) is a progressive degenerative joint disease which results in chronic degeneration of articular cartilage and sclerosis of bone. While tendons and ligaments may heal to a limited extent, articular cartilage has poor intrinsic regenerative potential, and critical-sized bone defects and pathological fractures cannot regenerate spontaneously. OA represents a significant burden of disease globally, affecting 240 million people in the world. The objective of tissue engineering is to recapitulate the natural healing cascade and developmental process by transplanting stromal and progenitor cells which can act directly or indirectly. As the ultimate goal of regenerative medicine is to avoid in vitro expansion of cells and its associated complications, the adipose-derived stromal cell (ASC) is an attractive progenitor cell for tissue engineering for treatment of OA. While clinical studies are still in their infancy, ASCs together with novel scaffold materials represent promising treatment options for patients suffering from OA. How ASCs exert their regenerative potential is a topic of debate, whereby it may be a result of direct differentiation of ASCs into the desired regenerating tissue, and/or through paracrine activity. With the advancement of material science, it is increasingly possible to enhance engraftment of ASCs through the use of biomaterials or to direct progenitor cell fate by activating biophysical signals through designed material microstructures. There are currently over 180 completed or ongoing registered early stage clinical trials involving ASCs, with 17 completed studies reviewed herein detailing the use of ASCs in OA. In order for ASC therapy to become an "off-the-shelf" option for treating OA, several strategies are currently being explored such as ASC cryopreservation and use of allogeneic ASCs. Newer approaches, such as exosome therapy, allow for the use of acellular ASC-derived therapies and are also currently the focus of ongoing investigations.

Project description:The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Immunohistostaining of intact adipose tissue was used to identify three markers (CD31, CD34, and CD146), which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90 and CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture, and tested for adipogenesis. The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/alpha-SMA+/CD90+/-/CD34-/CD31-; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146-/alpha-SMA-/CD90+/CD34+/CD31-. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), whereas small vessel endothelium was CD31+/CD34-/CD90- (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31- pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared with unsorted expanded SVF cells. In adipose tissue, perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34- pericytes, and the outermost of CD146-/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD34+ subset detected by flow cytometry at low frequency suggests a population transitional between pericytes and SA-ASC.

Dataset Information

A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue.

Publications

A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue.

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