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Inflammation, Innate Immunity, and the Intestinal Stromal Cell Niche: Opportunities and Challenges.

Owens BM - Front Immunol (2015)

Bottom Line: However, unlike hematopoietic immune cells, tissue stromal cell populations remain poorly characterized with respect to specific surface marker expression, their ontogeny, self-renewal, and proliferative capacity within tissues and the extent to which they undergo phenotypic immunological changes during the course of an infectious or inflammatory insult.Extending our knowledge of the immunological features of stromal cells provides an exciting opportunity to further dissect the underlying biology of many important immune-mediated diseases, although several challenges remain in bringing the emerging field of stromal immunology to equivalence with the study of the hematopoietic immune cell compartment.This review highlights recent studies that have begun unraveling the complexity of tissue stromal cell function in immune responses, with a focus on the intestine, and proposes strategies for the development of the field to uncover the great potential for stromal immunology to contribute to our understanding of the fundamental pathophysiology of disease, and the opening of new therapeutic avenues in multiple chronic inflammatory conditions.

View Article: PubMed Central - PubMed

Affiliation: Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford , Oxford , UK ; Somerville College, University of Oxford , Oxford , UK.

ABSTRACT
Stromal cells of multiple tissues contribute to immune-mediated protective responses and, conversely, the pathological tissue changes associated with chronic inflammatory disease. However, unlike hematopoietic immune cells, tissue stromal cell populations remain poorly characterized with respect to specific surface marker expression, their ontogeny, self-renewal, and proliferative capacity within tissues and the extent to which they undergo phenotypic immunological changes during the course of an infectious or inflammatory insult. Extending our knowledge of the immunological features of stromal cells provides an exciting opportunity to further dissect the underlying biology of many important immune-mediated diseases, although several challenges remain in bringing the emerging field of stromal immunology to equivalence with the study of the hematopoietic immune cell compartment. This review highlights recent studies that have begun unraveling the complexity of tissue stromal cell function in immune responses, with a focus on the intestine, and proposes strategies for the development of the field to uncover the great potential for stromal immunology to contribute to our understanding of the fundamental pathophysiology of disease, and the opening of new therapeutic avenues in multiple chronic inflammatory conditions.

No MeSH data available.


Related in: MedlinePlus

Cell intrinsic and extrinsic innate immune functions of intestinal stromal cells. Human and murine intestinal stromal cells (iSCs), classified as CD45−EpCAM−CD31−CD90+(gp38+*)iCAM-1+VCAM-1+ cells display a capacity for the modulation of innate immune responses via several mechanisms. (i) iSCs express a diverse repertoire of TLRs and NLRs, allowing them to directly sense intact organisms, or their products. (ii) iSCs elaborate a range of cytokines upon encounter with foreign organisms. (iii) iSC-derived cytokines (e.g., GM-CSF) can modulate the function of professional innate immune cells; iSC-derived chemokines (e.g., CCL2) can recruit professional innate immune cells. (iv) iSCs can phagocytose and internalize bacteria, and process exogenous antigen. (v) iSCs express HLA-DR and can functionally modulate effector and regulatory T cell populations. The innate functions of iSCs are – in general – less efficient than in myeloid cells, and lead to the designation of iSCs as “non-professional innate immune cells.” *Currently only determined in murine systems.
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Figure 1: Cell intrinsic and extrinsic innate immune functions of intestinal stromal cells. Human and murine intestinal stromal cells (iSCs), classified as CD45−EpCAM−CD31−CD90+(gp38+*)iCAM-1+VCAM-1+ cells display a capacity for the modulation of innate immune responses via several mechanisms. (i) iSCs express a diverse repertoire of TLRs and NLRs, allowing them to directly sense intact organisms, or their products. (ii) iSCs elaborate a range of cytokines upon encounter with foreign organisms. (iii) iSC-derived cytokines (e.g., GM-CSF) can modulate the function of professional innate immune cells; iSC-derived chemokines (e.g., CCL2) can recruit professional innate immune cells. (iv) iSCs can phagocytose and internalize bacteria, and process exogenous antigen. (v) iSCs express HLA-DR and can functionally modulate effector and regulatory T cell populations. The innate functions of iSCs are – in general – less efficient than in myeloid cells, and lead to the designation of iSCs as “non-professional innate immune cells.” *Currently only determined in murine systems.

Mentions: Far from being merely passive structural entities, stromal cell populations exhibit a capacity for diverse cell-intrinsic and -extrinsic immune function in many non-lymphoid tissues, including the intestine (2). These newly appreciated immune functions are reminiscent of those now well described for intestinal epithelial cells, which for a long time were also considered to be “non-immune” cells (3). Distinct from both epithelial and hematopoietic cell lineages (Table 1), stromal cells are a heterogeneous group of cells derived from mesenchymal progenitors that constitute a major component of the intestinal mucosa (4). We recently revealed a mechanism for innate sensing of pathogenic bacteria by primary human colonic CD45−EpCAM−CD31−CD90+ stromal cells (5), supporting previous data derived from human iSC lines (6) and murine infection models (7) that together suggest that tissue stromal cells can act as sentinel innate immune populations within the intestine. In line with others, we proposed that iSCs are designated as “Non-professional innate immune cells” (Figure 1) (5, 8–10). This reflects their capacity for innate sensing of bacteria (and possibly other organisms) via TLRs/NLRs, their potential to express HLA-DR/MHCII, and their ability to support/modulate the function of T cell populations, including regulatory T cells (Tregs) (11). Despite these cardinal features of innate immune cell populations, it is clear that the functional ability to take up, process and present foreign antigen is more limited for iSCs than in prototypic “professional” innate immune cells, such as macrophages, dendritic cells, and monocytes (5, 9). In addition, levels of innate immune (TLR) receptor expression in iSCs appear to be lower than in epithelial cell populations from the human intestine (12).


Inflammation, Innate Immunity, and the Intestinal Stromal Cell Niche: Opportunities and Challenges.

Owens BM - Front Immunol (2015)

Cell intrinsic and extrinsic innate immune functions of intestinal stromal cells. Human and murine intestinal stromal cells (iSCs), classified as CD45−EpCAM−CD31−CD90+(gp38+*)iCAM-1+VCAM-1+ cells display a capacity for the modulation of innate immune responses via several mechanisms. (i) iSCs express a diverse repertoire of TLRs and NLRs, allowing them to directly sense intact organisms, or their products. (ii) iSCs elaborate a range of cytokines upon encounter with foreign organisms. (iii) iSC-derived cytokines (e.g., GM-CSF) can modulate the function of professional innate immune cells; iSC-derived chemokines (e.g., CCL2) can recruit professional innate immune cells. (iv) iSCs can phagocytose and internalize bacteria, and process exogenous antigen. (v) iSCs express HLA-DR and can functionally modulate effector and regulatory T cell populations. The innate functions of iSCs are – in general – less efficient than in myeloid cells, and lead to the designation of iSCs as “non-professional innate immune cells.” *Currently only determined in murine systems.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4471728&req=5

Figure 1: Cell intrinsic and extrinsic innate immune functions of intestinal stromal cells. Human and murine intestinal stromal cells (iSCs), classified as CD45−EpCAM−CD31−CD90+(gp38+*)iCAM-1+VCAM-1+ cells display a capacity for the modulation of innate immune responses via several mechanisms. (i) iSCs express a diverse repertoire of TLRs and NLRs, allowing them to directly sense intact organisms, or their products. (ii) iSCs elaborate a range of cytokines upon encounter with foreign organisms. (iii) iSC-derived cytokines (e.g., GM-CSF) can modulate the function of professional innate immune cells; iSC-derived chemokines (e.g., CCL2) can recruit professional innate immune cells. (iv) iSCs can phagocytose and internalize bacteria, and process exogenous antigen. (v) iSCs express HLA-DR and can functionally modulate effector and regulatory T cell populations. The innate functions of iSCs are – in general – less efficient than in myeloid cells, and lead to the designation of iSCs as “non-professional innate immune cells.” *Currently only determined in murine systems.
Mentions: Far from being merely passive structural entities, stromal cell populations exhibit a capacity for diverse cell-intrinsic and -extrinsic immune function in many non-lymphoid tissues, including the intestine (2). These newly appreciated immune functions are reminiscent of those now well described for intestinal epithelial cells, which for a long time were also considered to be “non-immune” cells (3). Distinct from both epithelial and hematopoietic cell lineages (Table 1), stromal cells are a heterogeneous group of cells derived from mesenchymal progenitors that constitute a major component of the intestinal mucosa (4). We recently revealed a mechanism for innate sensing of pathogenic bacteria by primary human colonic CD45−EpCAM−CD31−CD90+ stromal cells (5), supporting previous data derived from human iSC lines (6) and murine infection models (7) that together suggest that tissue stromal cells can act as sentinel innate immune populations within the intestine. In line with others, we proposed that iSCs are designated as “Non-professional innate immune cells” (Figure 1) (5, 8–10). This reflects their capacity for innate sensing of bacteria (and possibly other organisms) via TLRs/NLRs, their potential to express HLA-DR/MHCII, and their ability to support/modulate the function of T cell populations, including regulatory T cells (Tregs) (11). Despite these cardinal features of innate immune cell populations, it is clear that the functional ability to take up, process and present foreign antigen is more limited for iSCs than in prototypic “professional” innate immune cells, such as macrophages, dendritic cells, and monocytes (5, 9). In addition, levels of innate immune (TLR) receptor expression in iSCs appear to be lower than in epithelial cell populations from the human intestine (12).

Bottom Line: However, unlike hematopoietic immune cells, tissue stromal cell populations remain poorly characterized with respect to specific surface marker expression, their ontogeny, self-renewal, and proliferative capacity within tissues and the extent to which they undergo phenotypic immunological changes during the course of an infectious or inflammatory insult.Extending our knowledge of the immunological features of stromal cells provides an exciting opportunity to further dissect the underlying biology of many important immune-mediated diseases, although several challenges remain in bringing the emerging field of stromal immunology to equivalence with the study of the hematopoietic immune cell compartment.This review highlights recent studies that have begun unraveling the complexity of tissue stromal cell function in immune responses, with a focus on the intestine, and proposes strategies for the development of the field to uncover the great potential for stromal immunology to contribute to our understanding of the fundamental pathophysiology of disease, and the opening of new therapeutic avenues in multiple chronic inflammatory conditions.

View Article: PubMed Central - PubMed

Affiliation: Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford , Oxford , UK ; Somerville College, University of Oxford , Oxford , UK.

ABSTRACT
Stromal cells of multiple tissues contribute to immune-mediated protective responses and, conversely, the pathological tissue changes associated with chronic inflammatory disease. However, unlike hematopoietic immune cells, tissue stromal cell populations remain poorly characterized with respect to specific surface marker expression, their ontogeny, self-renewal, and proliferative capacity within tissues and the extent to which they undergo phenotypic immunological changes during the course of an infectious or inflammatory insult. Extending our knowledge of the immunological features of stromal cells provides an exciting opportunity to further dissect the underlying biology of many important immune-mediated diseases, although several challenges remain in bringing the emerging field of stromal immunology to equivalence with the study of the hematopoietic immune cell compartment. This review highlights recent studies that have begun unraveling the complexity of tissue stromal cell function in immune responses, with a focus on the intestine, and proposes strategies for the development of the field to uncover the great potential for stromal immunology to contribute to our understanding of the fundamental pathophysiology of disease, and the opening of new therapeutic avenues in multiple chronic inflammatory conditions.

No MeSH data available.


Related in: MedlinePlus