TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.
Animals ; Antibodies/blood ; Antibody Formation/immunology ; Antibody Specificity/immunology ; Antigen-Presenting Cells/*immunology ; Antigens, CD1d/immunology ; Arthritis, Experimental/blood/*immunology/*prevention & control ; Collagen Type II/immunology ; Cytokines/blood ; Immune Tolerance/*immunology ; Inflammation Mediators/blood ; Mice ; Natural Killer T-Cells/*immunology ; Th1 Cells/immunology

OBJECTIVETo investigate the immunoregulation effects of umbilical cord mesenchymal stem cells (UC-MSCs) on the rats with collagen II induced arthritis (CIA).

METHODSThe rats were first immunized by intradermal injection of chicken collagen type II emulsified with complete Freund's adjuvant (CFA) to monitor their swelling of foot, hair color and action state. After injected UC-MSC by caudal vein, the rats were scored with the arthritis index (AI) once a week. Then, the concentration of interleukin (IL-6), tumor necrosis factor-α (TNF-α) in serum and D-dimer (D-D), antithrombin-III (AT-III), thrombomodulin (TM) in plasma were detected by ELISA.

RESULTSObvious swellings of the feet were found in the experiment group compared with normal one. ELISA analysis showed that the concentrations of IL-6, TNF-α, D-D and TM in plasma of the experiment group as of (200.48 ± 15.04) ng/L, (450.25 ± 45.39) ng/L, (274.26 ± 67.93) ng/L and (9.18 ± 0.84) µg/L, respectively were higher than of(167.62 ± 0.97) ng/L, (371.44 ± 21.26) ng/L, (193.95 ± 8.22) ng/L and (6.30 ± 0.32) µg/L respectively in normal group (P < 0.05), but the concentration of AT-III \[(89.57 ± 6.40) ng/L\] was lower than normal group \[(112.82 ± 1.74) ng/L\] (P < 0.05). The levels of cytokines through the UC-MSCs treatment were significantly different from the model group (P < 0.05). After 9 weeks, these cytokines in the UC-MSCs group were mostly the same as the normal group.

CONCLUSIONThe thrombophilia status of the CIA rats was caused by immune injury. The UC-MSCs reduced the production of inflammatory cytokines and regulated and repaired the balance of coagulation and anticoagulation system of the body to cure the immune-related thrombophilia.

Animals ; Antithrombins ; blood ; Arthritis, Experimental ; immunology ; physiopathology ; prevention & control ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Inflammation ; Interleukin-6 ; blood ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; prevention & control ; Tumor Necrosis Factor-alpha ; blood ; Umbilical Cord ; cytology

OBJECTIVETo investigate the effects of oral administration of type II collagen (CII) on adjuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CII with those of the Chinese traditional medicine Tripterygium Polyglycoside administered similarly.

METHODSArthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CII or Tripterygium Polyglycoside, changes in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, including delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycobacterium tuberculosis (MT) antibody in serum, and levels of IFN-gamma and TNF-alpha in articular steep in rats.

RESULTSOral administration of CII was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CII were stronger than those by Tripterygium Polyglycoside. Oral administration of CII inhibited antigen-specific immune response, such as DTH and antibody reaction to CII. In addition, the expression of IFN-gamma and TNF-alpha in joints were locally downregulated.

CONCLUSIONSThe therapeutic effect of oral administration of CII is obvious on adjuvant arthritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-gamma and TNF-alpha, and the suppression of cell immunity.

Administration, Oral ; Animals ; Antibodies ; blood ; Arthritis, Experimental ; drug therapy ; immunology ; Collagen Type II ; therapeutic use ; Hypersensitivity, Delayed ; prevention & control ; Immune Tolerance ; Interferon-gamma ; biosynthesis ; Male ; Mycobacterium tuberculosis ; immunology ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; pathology ; Tripterygium ; Tumor Necrosis Factor-alpha ; biosynthesis