Festschrift Maternal autoimmune disease influences self-tolerance in offspring: The role of suppressor cells and materno-foetal cell traffic

Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.

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Role of myeloid-derived suppressor cells in autoimmune disease

World Journal of Immunology ◽

10.5411/wji.v4.i1.26 ◽

2014 ◽

Vol 4 (1) ◽

pp. 26 ◽

Cited By ~ 43

Author(s):

Kristen R Crook

Keyword(s):

Autoimmune Disease ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells

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C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

Cell Death and Disease ◽

10.1038/s41419-021-04052-5 ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Dan Li ◽

Li Lu ◽

Wei Kong ◽

Xiaoyu Xia ◽

Yuchen Pan ◽

...

Keyword(s):

Autoimmune Disease ◽

Lupus Erythematosus ◽

Nuclear Transfer ◽

Suppressor Cells ◽

Target Cells ◽

Lectin Receptors ◽

Lectin Receptor ◽

And Function

AbstractRecent studies indicate that Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) can function as the signal of pattern recognition receptors, which play a pivotal role in the pathogenesis of the autoimmune disease. Systemic lupus erythematosus (SLE) is a classic autoimmune disease. Previous reports mainly focused on the potential role of TLRs in regulating the development of SLE, but little is known about the role of CLRs in the progression of SLE. Our previous studies showed that the inflammation-mediated accumulation of myeloid-derived suppressor cells (MDSCs) including granulocytic (G-MDSCs) and monocytic (M-MDSCs) participated in the pathogenesis of lupus. Mice deficient in Card9 (the downstream molecule of CLRs) were more susceptible to colitis-associated cancer via promoting the expansion of MDSCs. Whether the abnormal activation of CLRs regulates the expansion of MDSCs to participate in the pathogenesis of lupus remains unknown. In the present study, the expressions of CLRs were examined in both SLE patients and mouse models, revealing the expression of Dectin3 was positively correlated with SLEDAI. Dectin3 deficiency retarded the lupus-like disease by regulating the expansion and function of MDSCs. The mechanistic analysis revealed that Dectin3 deficiency promoted FoxO1-mediated apoptosis of MDSCs. Syk-Akt1-mediated nuclear transfer of FoxO1 increased in Dectin3-deficient MDSCs. Notedly, the accumulation of M-MDSCs mainly decreased in Dectin3−/− lupus mice, and the nuclear transfer of FoxO1 negatively correlated with the expression of LOX-1 on M-MDSCs. The silencing of FoxO1 expression in Dectin3−/− mice promoted the expansion of LOX-1+ M-MDSCs in vivo, and LOX-1+ M-MDSCs increased the differentiation of Th17 cells. Both LOX-1 expression on M-MDSCs and Dectin3 expression on MDSCs increased in patients with SLE. These data indicated that increased LOX-1+ M-MDSCs were related to the exacerbation of SLE development and might be potential target cells for the treatment of SLE.

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Faculty Opinions recommendation of Essential role of CCL21 in establishment of central self-tolerance in T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727717098.793536378 ◽

2017 ◽

Author(s):

Jens V Stein

Keyword(s):

T Cells ◽

Essential Role ◽

Self Tolerance

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Deciphering the Role of microRNAs in Regulation of Immune Surveillance, Self-Tolerance and Allograft Transplant Outcome

Current Stem Cell Research & Therapy ◽

10.2174/1574888x11666160201120129 ◽

2018 ◽

Vol 13 (5) ◽

pp. 336-344

Author(s):

Cherry S. Leung ◽

Song Lu ◽

Jiatao Li ◽

William KK Wu ◽

Kathy O. Lui

Keyword(s):

Immune Surveillance ◽

Transplant Outcome ◽

Self Tolerance

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Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

Journal of Environmental and Public Health ◽

10.1155/2012/619381 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Gerry K. Schwalfenberg

Keyword(s):

Rheumatoid Arthritis ◽

Multiple Sclerosis ◽

Inflammatory Bowel Disease ◽

Vitamin D ◽

Type 1 Diabetes ◽

Autoimmune Disease ◽

Solar Radiation ◽

Inflammatory Bowel

This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

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Concomitant autoimmunity may be a predictor of more severe stages of endometriosis

Scientific Reports ◽

10.1038/s41598-021-94877-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vanni Valeria Stella ◽

Villanacci Roberta ◽

Salmeri Noemi ◽

Papaleo Enrico ◽

Delprato Diana ◽

...

Keyword(s):

Autoimmune Disease ◽

Adaptive Immune System ◽

Stage Iv ◽

Multivariate Logistic Regression Model ◽

Medical Patients ◽

Laparoscopic Procedures ◽

Logistic Analysis ◽

Increased Risk ◽

History Of

AbstractPathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p < 0.001) and the number of laparoscopic procedures performed (OR 2.81, 95% CI 1.45–5.43, p = 0.002) emerged as factors significantly associated with the likelihood of stage IV endometriosis. In the multivariate logistic regression model, concomitant autoimmunity remained a significant predictor of stage IV endometriosis (OR 2.54, 95% CI 1.57–4.10, p = 0.004), whereas the association between the number of laparoscopic procedures performed and stage IV endometriosis was found to be of borderline-significance (OR 2.70, 95% 1.37–5.30, p = 0.050). Our findings suggest that endometriosis is more severe in patients who are also affected by autoimmune disturbances after controlling for relevant confounders.

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AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2972 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1484.1-1484

Author(s):

S. Ahmed ◽

E. Nikiphorou ◽

J. Bayliss

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factor ◽

Autoimmune Disease ◽

Environmental Risk ◽

Narrative Review ◽

Environmental Risk Factor ◽

T Helper ◽

Dietary Salt ◽

Salt Consumption

Background:The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt.Objectives:To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA.Methods:A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer.Results:Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further.Conclusion:This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA.Disclosure of Interests:None declared

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