Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 18:14:1085448.
doi: 10.3389/fimmu.2023.1085448. eCollection 2023.

AIM2 and Psoriasis

Yuxi Zhang  1   2   3   4 , Xiaoqing Xu  1   2   3   4 , Hui Cheng  1   2   3   4 , Fusheng Zhou  1   2   3   4
Affiliations
Review

AIM2 and Psoriasis

Yuxi Zhang et al. Front Immunol. .

Abstract

Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (AIM2), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.

Keywords: AIM2; epigenetic; inflammasome; keratinocytes; psoriasis; trained immunity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Characteristics of AIM2 inflammasome. (A) Structure of AIM2 inflammasome. (B) Genetic regulation and epigenetic regulation of AIM2. (C) Relationship between cGAS-STING pathway and AIM2 inflammasome. (D) Relationship between JAK-STAT pathway and AIM2 inflammasome in macrophages linked by autocrine secretion of IFN-γ. (E) Relationship between JAK-STAT pathway and AIM2 inflammasome in keratinocytes after JAK inhibitor application. JAK-STAT and cGAS-STING pathway are linked through the autocrine of IFN-γ. (F) Some non-immune cells mediating inflammation through AIM2 inflammasome. (G) Some immune cells mediating inflammation through AIM2 inflammasome. (H) Skin epithelial stem cells are involved in trained immunity through AIM2 inflammasome and the downstream inflammatory cytokine IL-1β. AIM2 integrates the trained immune memory properties of immune cells with non-immune cells.
Figure 2
Figure 2
The inflammasome-independent way of AIM2. (A) Regulatory role of AIM2 in cell proliferation. A1, A2: AIM2 promotes keratinocytes proliferation through the Wnt5a pathway; PI3K/AKT pathway promotes keratinocytes and osteosarcoma cells proliferation, but AIM2 inhibits it. A3: AIM2 inhibits the proliferation of intestinal stem cells by suppressing the Wnt pathway, AIM2 activates PI3K/AKT pathway via Wnt5a and promotes intestinal stem cell proliferation. A4: AIM2 promotes gastric carcinoma cell proliferation through MAPK pathway. A5: AIM2 put a curb on epithelial stem cells proliferation in glomerulonephritis. (B) Role of AIM2 in Treg cells function/development/differentiation. AIM2 interacts with RACK1-PP2A protein to inhibit AKT/mTOR pathway, leading to metabolite changes that regulate Treg function and stability; AIM2 inhibits Treg proliferation through ERK1/2 pathway or by inhibiting PI3K/AKT pathway. (C) AIM2 forms a complex named AIM2 PANoptosome with pyrin, ASC and ZBPI, which mediates inflammatory cell death and cytokine release.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Boehncke W-H, Schön MP. Psoriasis. Lancet (2015) 386:983–94. doi: 10.1016/S0140-6736(14)61909-7 - DOI - PubMed
    1. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci (2019) 20:1475. doi: 10.3390/ijms20061475 - DOI - PMC - PubMed
    1. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: A review. JAMA (2020) 323:1945–60. doi: 10.1001/jama.2020.4006 - DOI - PubMed
    1. De Francesco MA, Caruso A. The gut microbiome in psoriasis and crohn’s disease: Is its perturbation a common denominator for their pathogenesis? Vaccines (Basel) (2022) 10:244. doi: 10.3390/vaccines10020244 - DOI - PMC - PubMed
    1. Hu SC-S, Lan C-CE. Psoriasis and cardiovascular comorbidities: Focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci (2017) 18:E2211. doi: 10.3390/ijms18102211 - DOI - PMC - PubMed

Publication types

Grants and funding

This work was supported by the Fund Project of National Natural Science Foundation of China (4601020204).