About this Research Topic
Adipose tissue harbors immune cells including macrophages and lymphocytes which contribute to chronic inflammation and metabolic dysfunctions, such as insulin resistance which occurs in obesity. However, previous research has been primarily focused on how macrophages change in phenotype and function in adipose tissues during the development of obesity. During obesity, macrophages become more pro-inflammatory, or M1-like, and Tregs become reduced in numbers and functionally suppressed. CD8+ T cells increase in number during obesity and are also associated with macrophage recruitment into adipose tissue, establishing an continuous cycle of inflammation. Furthermore, CD4+ T cells produce increased amounts of Th1 cytokines which contribute to this inflammatory state. However, the mechanisms underlying the effects on T cells in adipose tissue during obesity remain elusive.
Furthermore, increased CD8+ T cell numbers in adipose also occurs in HIV infection but the function of these T cells is currently unknown. In cancer, increased adipose establishes a chronic inflammatory state, but at the same time can reduce T cell function and thus may play an important role in tumor escape in vivo. The function of introduced CARs as therapy could also be affected by the toxic environment established by interactions of growing tumors with increased obesity.
In obesity, adipocytes are activated by TLRs established via chronic inflammation that arises from a gut breach, which is very similar to what happens in HIV infection. Adipocytes can thus become antigen presenters, but the antigens that T cells respond to in the adipose environment under these conditions are largely undescribed. In addition, as adipocytes intake more and more lipid in the obese state, the environment becomes hypoxic, leading to cell death. This can also occur in HIV, although anti-retroviral drugs are known to play a role in adipocyte mitochondrial toxicity. Similar toxicity could also occur with chemotherapies. During obesity, pre-adipocyte differentiation can become imbalanced with the increased need for lipid storage. This can result in adipose tissue that is depleted of both adipose and immune cells which then becomes fibrotic, a process that also occurs in HIV and cancer. The effects of this process on T cell function is unknown but is likely to alter T cell metabolism and eventually kill or drive away T cells.
Adipose tissue behaves differently in different depots. In obesity, the most inflammatory toxic adipose is visceral, so that in this tissue there are more inflammatory cytokines made by activated macrophages, Th-1 cells and activated CD8+ T cells. In HIV, visceral adiposity is associated with increased risk of morbidity and cardiovascular disease than subcutaneous adiposity. In cancer, visceral adiposity is also associated with greater cancer risk and more metastasis. In brown fat, the tissue is far more metabolically active with much less lipid storage and more features characteristic of lean adipose tissue including M2-type macrophages and increased numbers of Tregs. How brown fat and the related immune environment changes in obesity, HIV and cancer is also largely unknown in humans.
This Research Topic aims to examine T cell phenotypes and function in adipose tissue in normal situations, after obesity and in two other pertinent disease states, cancer and HIV infection. This Research Topic will serve to highlight new information, commonalities and differences between these conditions in order to light a path towards future research advances that could impact human health. We welcome the submission of Review, Mini-Review and Original Research articles encompassing human or animal model-based studies covering, but not limited to, the following topics:
1. The functions of specific T cells in adipose tissue including CD8+ T cells and Tregs.
2. The functions of lipid-specific NKT1 or NKT2 cells.
3. Antigen specificity of T cells in adipose tissue and disease-mediated alterations.
4. The mechanisms by which adipocytes alter T cell functions in situ.
5. Characterization of T cells in different adipose depots.
6. Comparison of T cells in visceral versus subcutaneous adipose tissue.
7. Bone marrow adipocyte niches and memory T cell function.
8. The influence of macrophages on T cell functions in adipose tissue.
9. The functions of innate T cells in adipose tissue.
Articles featuring studies on human adipose are highly encouraged. Articles based on mouse experiments with a human component are also encouraged.
Keywords: T cells, Adipose tissue, HIV, Obesity, Cancer
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