Adipose tissue aging is regulated by an altered immune system

Figures

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  Figure 1. In aging adipose tissue, dead adipocytes induce macrophages and DAMPs, thereby activating the NLRP3 inflammasome in adipocytes. FFA and LPS combine TLR on adipocytes and activate NFκB. Hypoxia and mechanical stress can also activate NFκB. Adipocytes can produce proinflammatory cytokines and chemokines, thus recruiting inflammatory cells and promoting the proinflammatory polarization of recruited immune cells. FFA free fatty acid, LPS lipopolysaccharide, TLR toll-like receptor, DAMP damage-associated molecular patterns, NLR NOD-like receptor.

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  Figure 2. Interactions among adipocytes, NK cells and ILCs (mediated by NKp46 ligands, expressed by stressed adipocytes) lead to further exacerbated expression of IFN-γ, TNF-α, and IL-6. Since macrophages are triggered by such proinflammatory cytokines, IL-12 and IL-15 are consequently secreted by macrophages to induce NK-cell and ILC proliferation. CD11b on neutrophils and ICAM1 on adipocytes mediate their interaction.

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  Figure 3. In aging adipose tissues, the number of conventional T cells, γδT cells, increases, thus contributing to adipose tissue inflammation. CD28+ T memory cells are converted to CD4+ CD62- memory T cells. FFA induces the expression of MHC-II through the JAK/STAT1 signaling pathway, facilitating antigen presentation to CD4+ T cells. CD40/TRAF2/3/5/6 signaling is critical for CD8+ T-cell-induced inflammation. B2 cells are recruited to FALC by LTB4, and CXCR5 on B2 cells is important for their recruitment to FALC. Some B2 cells become ABCs. B2 cells and ABC are proinflammatory, producing IgG and exacerbating inflammation in adipose tissue. FFA free fatty acid, FALC fat-associated lymphoid cluster, LTB4 leukotriene B4, CXCR5 C-X-C chemokine receptor type 5.

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  Figure 4. M2 macrophages, DCregs, Tregs, eosinophils, and iNKT cells are significant anti-inflammatory immune cells in adipose tissue, and their abundance is mostly decreased in aging adipose tissue. Cell–cell interactions are essential for adipose tissue homeostasis. ILC2s can promote the proliferation of eosinophils and M2 macrophages, and eosinophils can promote the proliferation of M2 macrophages through IL-4. iNKT cells can promote the proliferation of M2 macrophages through IL-4 and IL-10. B1 cells produce IgM, which exerts anti-inflammatory effects and promotes the proliferation of M2 macrophages.

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  Figure 5. The MAPK signaling pathway is critical for the expression of MHC-II in DCs. JNK signaling can interact with IRS to reduce PI3K/AKT signaling and contribute. JNK can further promote AP-1 production and promote inflammation in adipose tissue. The NF-κB signaling pathway mediates the production of IL-1β in neutrophils and the activation of ILC2s. This pathway is also essential for the adipocyte response to TNF and the production of CCL2. Wnt signaling mediates IL-10 production in CDC1s and binds TLR to produce proinflammatory cytokines in macrophages. Wnt5a can induce JNK in adipocytes. The JAK/STAT signaling pathway is essential for activating peripheral blood B cells and the proliferation of ILC1s. This pathway is also critical for the adipocyte response to IFN-γ. STATs can further bind IRFs to induce the production of proinflammatory cytokines. The AMPK signaling pathway mediates the proliferation of M2-type macrophages and blocks the proinflammatory signaling pathway in adipocytes. However, it may cause a decrease in the function of ILC2s. AP-1 activator protein 1, CCL2 chemokine ligand 2, TLR toll-like receptor, IRF interferon regulation factor.