Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4 + CD8 + T suppressor cells that protect from collagen-induced arthritis (CIA)

Marcińska, Katarzyna; Majewska‐Szczepanik, Monika; Lazar, Agata; Kowalczyk, Paulina; Biała, Dominika; Woźniak, Dorota; Szczepanik, Marian

doi:10.1016/j.pharep.2015.11.004

Cited by 9 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been well documented that CD4 + T cells are required for the induction of CIA, whereas CD8 + T cells exhibit a suppressive role (38,39). The proportion of CD4 + T cells was significantly increased, whereas the proportion of CD8 + T cells was decreased in patients with RA (40). Consistent with these facts, our results showed that GdX-KO mice under CII treatment developed less inflammation with fewer CD4 + T cells and more CD8 + T cells, whereas the WT CIA mice owned reversed populations of T cells.…”

Section: Discussionmentioning

confidence: 98%

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells

Liu

Wang

et al. 2019

FASEB j.

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (Th)‐1 and Th17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how Thl and Th17 cells are regulated during RA. In this study, we report that the small ubiquitin‐like protein X‐linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of Th17 and regulatory T (Treg) cells during collagen‐induced arthritis (CIA). We discovered that the splenocytes of GdX‐knockout (KO) mice were insensitive to T‐cell stimulants. Correspondingly, GdX‐KO mice showed alleviative Th1‐mediated delayed‐type hypersensitivity and were resistant to CIA compared with wild‐type mice. GdX‐KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti‐collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the Th1 and Th17 differentiation but increased the Treg cell proliferation. Consistently, deletion of GdX decreased the transcription level of T‐cell‐specific T‐box transcription factor and RAR‐related orphan receptor‐γ transcription factor but increased that of forkhead box P3 after being challenged with type‐II collagen. These findings suggested that GdX functions as an important regulator of Th1 or Th17 and Treg cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.—Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C, Li, J., Ju, Y., Chang, Z. GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of Th1/Th17 and regulatory T cells. FASEB J. 33, 8375–8385 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 98%

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells

Liu

Wang

et al. 2019

FASEB j.

View full text Add to dashboard Cite

show abstract

“…According to a 5-point scale, the Arthritis index (AI) was calculated as follows: 0 = no evidence of erythema and swelling; 1 = mild erythema and swelling of the wrist or ankle; 2 = moderate erythema and swelling from the wrist to the metacarpal joints or from the ankle to the metatarsal joints; 3 = severe erythema and swelling of the entire paw including the digits and 4 = maximal erythema and swelling of the paw, or ankylosis of the limb. The total AI was the sum of the scores for each of the four limbs (Marcinska et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Dynamic Alterations in the Gut Microbiota of Collagen-Induced Arthritis Rats Following the Prolonged Administration of Total Glucosides of Paeony

Peng

Xie

et al. 2019

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a common autoimmune disease linked to chronic inflammation. Dysbiosis of the gut microbiota has been proposed to contribute to the risk of RA, and a large number of researchers have investigated the gut-joint axis hypothesis using the collagen-induced arthritis (CIA) rats. However, previous studies mainly involved short-term experiments; very few used the CIA model to investigate changes in gut microbiota over time. Moreover, previous research failed to use the CIA model to carry out detailed investigations of the effects of drug treatments upon inflammation in the joints, hyperplasia of the synovium, imbalance in the ratios of Th1/Th2 and Th17/Treg cells, intestinal cytokines and the gut microbiota following long-term intervention. In the present study, we carried out a 16-week experiment to investigate changes in the gut microbiota of CIA rats, and evaluated the modulatory effect of total glucosides of paeony (TGP), an immunomodulatory agent widely used in the treatment of RA, after 12 weeks of administration. We found that taxonomic differences developed in the microbial structure between the CIA group and the Control group. Furthermore, the administration of TGP was able to correct 78% of these taxonomic differences, while also increase the relative abundance of certain forms of beneficial symbiotic bacteria. By the end of the experiment, TGP had reduced body weight, thymus index and inflammatory cell infiltration in the ankle joint of CIA rats. Furthermore, the administration of TGP had down-regulated the synovial content of VEGF and the levels of Th1 cells and Th17 cells in CIA rats, and up-regulated the levels of Th2 cells and Treg cells. The administration of TGP also inhibited the levels of intestinal cytokines, secretory immunoglobulin A (SIgA) and Interferon-γ (IFN-γ). In conclusion, the influence of TGP on dynamic changes in gut microbiota, along with the observed improvement of indicators related to CIA symptoms during 12 weeks of administration, supported the hypothesis that the microbiome may play a role in TGP-mediated therapeutic effects in CIA rats. The present study also indicated that the mechanism underlying these effects may be related to the regulation of intestinal mucosal immunity remains unknown and deserves further research attention.

show abstract

“…A recent clinical trial showed reduced signs of disease activity in relapsing–remitting MS patients treated with a transdermal application of a mixture of myelin peptides containing MBP85-99, MOG35-55, and PLP139-155 ( 21 ). Efficacy of specific skin-induced tolerance was also demonstrated in collagen-induced arthritis ( 22 ) and inflammatory bowel disease ( 23 ). The effectiveness of these strategies has been correlated with the presence of tolerogenic dendritic cells (DCs) and Tregs expansion.…”

Section: Introductionmentioning

confidence: 99%

Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

Zorzella-Pezavento¹,

Mimura²,

Fraga-Silva³

et al. 2017

Front. Immunol.

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely employed to evaluate new strategies to control MS, including procedures to induce immunological tolerance. Considering that skin exposure to protein antigens can induce tolerance and that vitamin D analogs conserve immunomodulatory potential and are less toxic, we investigated the efficacy of epicutaneous application of a myelin oligodendrocyte glycoprotein peptide (MOG35–55) associated with paricalcitol (PARI) on EAE development. Three and 11 days after EAE induction, C57BL/6 mice were treated with an occlusive patch containing MOG plus PARI. Clinical parameters were daily assessed, whereas immunological and histological evaluations were performed during the acute EAE phase. MOG and MOG + PARI significantly controlled disease development reducing weight loss and clinical score. Moreover, MOG and MOG + PARI reduced the inflammatory process and preserved the myelin sheath in the CNS. High percentages of Foxp3+ regulatory T cells (Tregs) and lower MHCII fluorescence intensity in dendritic cells in draining lymph nodes were concomitantly observed. MOG + PARI association was, however, more efficient being able to reduce disease incidence and clinical scores more significantly than MOG or PARI alone. This experimental group also displayed a higher ratio between mRNA expression for Foxp3 and RORc and a higher percentage of Foxp3+ cells in the CNS. Modulation of activation markers observed in microglial cells eluted from EAE treated mice were confirmed by in vitro studies with the BV-2 microglial cell line. The results show that MOG + PARI association applied by an epicutaneous route controlled EAE development. Protective involved mechanisms include mainly a higher proportion of Tregs and also a direct immunomodulatory effect of PARI on microglial cells.

show abstract

Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4 + CD8 + T suppressor cells that protect from collagen-induced arthritis (CIA)

Abstract: Maneuver of EC immunization with a protein antigen that induces suppressor cells to inhibit inflammatory responses may become an attractive, noninvasive, needle-free therapeutic method for different clinical situations.

Cited by 9 publications

References 28 publications

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells

Dynamic Alterations in the Gut Microbiota of Collagen-Induced Arthritis Rats Following the Prolonged Administration of Total Glucosides of Paeony

Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

Contact Info

Product

Resources

About

Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4 + CD8 + T suppressor cells that protect from collagen-induced arthritis (CIA)

Abstract: Maneuver of EC immunization with a protein antigen that induces suppressor cells to inhibit inflammatory responses may become an attractive, noninvasive, needle-free therapeutic method for different clinical situations.

Cited by 9 publications

References 28 publications

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells

Dynamic Alterations in the Gut Microbiota of Collagen-Induced Arthritis Rats Following the Prolonged Administration of Total Glucosides of Paeony

Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

Contact Info

Product

Resources

About

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells

GdX/UBL4A‐knockout mice resist collagen‐induced arthritis by balancing the population of T _h 1/T _h 17 and regulatory T cells