Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Zhong, Jianghong; Li, Qijing; Holmdahl, Rikard

doi:10.1016/j.jid.2021.01.006

Cited by 9 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-17A secretion from γδ T cells contributing to Ps-like inflammation was reported earlier by an intraperitoneal injection of mannan in ROS deficient BQ.Ncf1(m1j/m1j) mice ( 28 , 52 ) and the direct relevance of γδ T cells was later demonstrated using γδ T knockout mice crossed to this mouse strain ( 53 ). Interestingly, 17-β-estradiol treatment in C57BL/6 OVX mice was shown to modulate γδ T cells, a major source of IL-17 ( 54 ) and in the imiquimod-induced psoriasis model, estrogen aggravated the disease by enhancing IL-23 secretion from dendritic cells ( 42 ).…”

Section: Discussionmentioning

confidence: 68%

Estrogen Acts Through Estrogen Receptor-β to Promote Mannan-Induced Psoriasis-Like Skin Inflammation

Zeng

Wang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Sex-bias is more obvious in several autoimmune disorders, but not in psoriasis. However, estrogen levels fluctuate during puberty, menstrual cycle, pregnancy, and menopause, which are related to variations in psoriasis symptoms observed in female patients. Estrogen has disease promoting or ameliorating functions based on the type of immune responses and tissues involved. To investigate the effects of estrogen on psoriasis, at first, we developed an innate immunity dependent mannan-induced psoriasis model, which showed a clear female preponderance in disease severity in several mouse strains. Next, we investigated the effects of endogenous and exogenous estrogen using ovariectomy and sham operated mice. 17-β-estradiol (E2) alone promoted the skin inflammation and it also significantly enhanced mannan-induced skin inflammation. We also observed a prominent estrogen receptor-β (ER-β) expression in the skin samples, especially on keratinocytes. Subsequently, we confirmed the effects of E2 on psoriasis using ER-β antagonist (PHTPP) and agonist (DPN). In addition, estrogen was found to affect the expression of certain genes (vgll3 and cebpb), microRNAs (miR146a and miR21), and immune cells (DCs and γδ T cells) as well as chemokines (CCL5 and CXCL10) and cytokines (TNF-α, IL-6, IL-22, IL-23, and IL-17 family), which promoted the skin inflammation. Thus, we demonstrate a pathogenic role for 17-β-estradiol in promoting skin inflammation, which should be considered while designing new treatment strategies for psoriasis patients.

show abstract

Section: Discussionmentioning

confidence: 68%

Estrogen Acts Through Estrogen Receptor-β to Promote Mannan-Induced Psoriasis-Like Skin Inflammation

Zeng

Wang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The single-cell suspensions derived from spleens were analyzed with flow cytometry. Red blood cells were lysed with Ammonium-Chloride-Potassium (ACK) buffer to make single-cell suspensions [ 18 ]. Single-cell suspensions of the lymph nodes were generated through 40 μ m filters (Falcon cell strainer, Catalog No.…”

Section: Methodsmentioning

confidence: 99%

“…A blood sample of 30 μ L was collected from the submandibular facial vein for each mouse. Red blood cells were lysed with ammonium-chloride-potassium (ACK) buffer to make single-cell suspensions [ 18 ]. To prepare the samples, the glass-coverslip (Jingan, Shanghai, China) was coated with 5 μ g/mL of fibronectin (Sigma, Catalog No.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously found that a natural mutation in the Ncf1 gene impairs the formation of the NADPH oxidase 2 (NOX2) complex and the generation of reactive oxygen species (ROS) [ 1 , 12 ], promotes the proliferation of autoreactive CD4 T cells in spontaneous arthritis [ 13 , 14 ], enhances autoimmune encephalomyelitis in the absence of inducible nitric oxide [ 15 ], promotes the spread of psoriasis through innate production of interleukin 17 (IL-17) [ 16 , 17 , 18 ], activates STAT1 signaling in exaggerated lupus [ 19 ], and suppresses NETosis in neutrophils prepared from patients with the chronic granulomatous disease and autoimmune disorders [ 3 , 20 ]. 147-base pair of NET DNA is typically packed around a histone octamer composed of two copies of each of the histones H3, H4, H2A, and H2B [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles

Zhong

Zheng

Gao

et al. 2022

Heliyon

Self Cite

View full text Add to dashboard Cite

“…The perception of mannan by innate immune cells is complex and cell-type-specific [ 8 ]. Mannan was used to induce arthritis in various mice strains [ 7 , 8 , 9 , 10 , 11 , 12 ]. Injection of mannan in SKG mice resulted in about 4-week-earlier and more severe arthritis when compared to injection of zymosan A [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Phospholipase A1 Member A Deficiency Alleviates Mannan-Induced Psoriatic Arthritis in Mice Model

Zhao

Aoudjit

Bourgoin

2022

IJMS

View full text Add to dashboard Cite

Synovial fluids from rheumatoid and psoriatic arthritis patients have high levels of PLA1A. The current study was to understand PLA1A functions in the pathophysiology of rheumatic diseases. We generated Pla1a−/− mice to assess their phenotype and the impact of PLA1A deficiency on the development of mannan-induced psoriatic arthritis (MIP). Mice were evaluated routinely for the induced symptoms. On the day of sacrifice, blood samples were collected for hematology analysis and prepared for plasma. Livers were collected. Lymph node immune cells were analyzed using flow cytometry. We performed μCT scans of hind paws from naïve and mannan-induced female mice. Cytokines/chemokines were quantified using Luminex in hind paw tissues and plasma of female mice. Pla1a−/− mice showed a slight increase in circulating and lymph node lymphocytes. CD4+ T cells contributed most to this increase in lymph nodes (p = 0.023). In the MIP model, the lymph node ratios of CD3+ to CD19+ and CD4+ to CD8+ were higher in Pla1a−/− mice. Pla1a−/− mice were less susceptible to MIP (p < 0.001) and showed reduced bone erosions. Pla1a−/− mice also showed reduced IL-17, KC, IP-10, MIP-1β, LIF, and VEGF in hind paw tissues as compared to WT mice (p < 0.05). These findings indicated that PLA1A deficiency protected from the development of the MIP disease. The data suggested that PLA1A could contribute to MIP through increased activation of lymphocytes, possibly those producing IL-17.

show abstract

Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Cited by 9 publications

References 30 publications

Estrogen Acts Through Estrogen Receptor-β to Promote Mannan-Induced Psoriasis-Like Skin Inflammation

Estrogen Acts Through Estrogen Receptor-β to Promote Mannan-Induced Psoriasis-Like Skin Inflammation

Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles

Phospholipase A1 Member A Deficiency Alleviates Mannan-Induced Psoriatic Arthritis in Mice Model

Contact Info

Product

Resources

About