Trends in Immunology
Volume 38, Issue 7, July 2017, Pages 526-536
Journal home page for Trends in Immunology

Review
Immunological Functions of the Omentum

https://doi.org/10.1016/j.it.2017.03.002Get rights and content

Trends

VAT-associated Tregs are a transcriptionally and functionally unique population of Tregs that regulate immune responses and metabolic processes in adipose tissues, including the omentum.

ILC2 cells are found in adipose tissues like the omentum, where they regulate local immune responses and adipocyte metabolism.

The omentum is a well characterized site of ovarian cancer metastasis, due to its ability to collect tumor cells from the peritoneal cavity and to support tumor cell metabolism and growth.

Despite the immune functions of the omentum, it appears unable to promote adaptive immune response to tumors that implant in the milky spots.

The omentum is a visceral adipose tissue with unique immune functions. Although it is primarily an adipose tissue, the omentum also contains lymphoid aggregates, called milky spots (MSs), that contribute to peritoneal immunity by collecting antigens, particulates, and pathogens from the peritoneal cavity and, depending on the stimuli, promoting a variety of immune responses, including inflammation, tolerance, or even fibrosis. Reciprocal interactions between cells in the MS and adipocytes regulate their immune and metabolic functions. Importantly, the omentum collects metastasizing tumor cells and supports tumor growth by immunological and metabolic mechanisms. Here we summarize our current knowledge about the development, organization, and function of the omentum in peritoneal immunity.

Section snippets

Development of the Omentum and Milky Spots

The omentum (see Glossary) is a visceral adipose tissue (VAT) derived from mesothelial cells [1], connected to the spleen, stomach, pancreas, and colon 2, 3. Although well known as a visceral fat depot, the role of the omentum in peritoneal immunity was not recognized until the early 1900s, when a British surgeon referred to it as ‘the policeman of the abdomen’ due to its ability to attenuate peritonitis and promote surgical wound healing [4]. In fact, the omentum was noted to move about the

Structure of Omental Milky Spots

The leukocyte clusters in MSs are distinctly different from conventional secondary lymphoid tissues. For example, although the leukocytes in MSs are supported by a reticular network of fibroblastic stromal cells that can be observed using the ERTR-7 antibody [9], they lack identifiable follicular dendritic cells (FDCs) 9, 25. The B cell-attracting chemokine, CXCL13, which is associated with FDC networks in conventional lymphoid organs [26], is also strongly expressed in the MS [27]. However,

Cellular Composition of the Omentum and MSs

The leukocyte populations in MSs and other FALCs are also quite distinct from those in conventional lymphoid tissues 11, 27. B cells make up the majority of lymphocytes in MSs [9]. However, IgMhiIgDlo B1 cells outnumber IgMloIgDhi follicular B2 cells in MSs, whereas the opposite is true in conventional lymphoid organs 11, 20, 27, 36. B1 cells are generated by fetal-derived hematopoietic progenitors, some of which contribute to local B1 lymphopoiesis in the omenta of both mice and humans 37, 38.

Immune Responses in the Omentum

Consistent with its ability to collect antigens and cells from the peritoneal cavity, the MS of the omentum support both innate and adaptive immune responses to peritoneal antigens. For example, inflammation in the peritoneal cavity promotes the rapid migration of macrophages to the omentum – a process originally known as the macrophage disappearance reaction [60]. This process can be driven by sterile irritants, including LPS [61], zymosan [14], or thioglycollate [50], as well as inert

Peritoneal Tumor Metastasis in the Omentum

Primary tumors of the omentum are uncommon. However, the omentum is the most common site of peritoneal metastasis for some tumors, including gastrointestinal and ovarian carcinoma 28, 75, 76. In particular, ovarian cancer disseminates early and robustly to the omentum, where it is associated with poor prognosis and aggressive growth 10, 77, 78. Despite the fact that immune responses can be initiated in the MSs of the omentum, a protective immune response against tumors seems to not occur and

Concluding Remarks

We now understand that the immune activity of the omentum is highly specialized and that its unusual leukocyte composition has likely evolved to maintain adipocyte homeostasis, protect the unique environment of the peritoneal cavity and promote the differentiation of mucosal-homing cells that recognize gut antigens. Importantly, this model suggests that perturbations of omental functions that may occur in the context of obesity, tumor metastasis, peritoneal dialysis or most extremely,

Acknowledgments

This work was supported by NIH grant RO1-CA216234 to TDR and by the UAB Comprehensive Cancer Center P30-CA013148.

Glossary

Fat-associated lymphoid clusters (FALCs)
FALCs are similar to MSs in that they are clusters of leukocytes embedded in adipose tissue, primarily in mesenteric and pleural fat. However, FALCs are partially dependent on microbiota for their formation and are smaller and less frequent than the MSs of the omentum. Their function may be similar.
Mesothelial cells
a thin layer of cells that covers the omentum and other visceral and pleural organs. The surface of mesothelial cells is slippery to reduce

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