Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases.
  The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-κB may explain these effects of thalidomide. NF-κB is retained in the cytoplasm with IκBα, and is activated by a wide variety of inflammatory stimuli including TNF, IL-1 and endotoxin followed by its translocation to the nucleus. Angiogenesis and organogenesis also require gene transcription and signal translocation. The findings shed new light on the anti-inflammatory properties of thalidomide and suggest pharmaceutical actions of thalidomide via interference of transcription mechanism. I reviewed the effects of thalidomide on auto-inflammatory diseases of childhood.

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  Regulatory B cells that produce IL-10 are now recognized as an important component of the immune system. Hallmark papers from a number of distinguished laboratories have identified phenotypically diverse B cell subsets with regulatory functions during distinct autoimmune diseases, including IL-10-producing B cells, CD5⁺ B-1a cells, CD1d⁺ marginal zone B cells, and transitional 2-marginal zone precursor B cells. Most recently, a numerically rare and phenotypically unique CD1d^hiCD5⁺CD19^hi subset of regulatory B cells has been identified in the spleens of both normal and autoimmune mice. Remarkably, regulatory B cells are potent negative regulators of inflammation and autoimmunity in mouse models of disease in vivo. Herein, our current understanding of regulatory B cell function is reviewed in the context of previous studies that have identified and characterized regulatory B cells.

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  Adhesion molecules are critical for leukocytes migration to the skin. Leukocytes must first be captured or tethered from the flowing blood allowing them to roll along the skin vessels. Leukocytes are activated by chemoattractants, which results in firm adhesion and arrest and ultimately transendothelial migration into the tissue. Selectin family which consists of L-selectin, P-selectin, E-selectin is critical for capture and rolling. Deficiency of these molecules leads to the diminution of cutaneous inflammation. Firm adhesion is governed by β2 integrin and α4 integrin. Inhibition of β2 integrin and its ligand ICAM-1 also reduce cutaneous inflammation. Similarly, blocking of α4 integrin and its ligand VCAM-1 alleviate inflammation of the skin. Transmigration and diapedesis are mediated by various molecules such as PECAM-1, CD99, and JAM, whose inhibition also leads to amelioration of skin inflammation. Manipulating adhesion molecules might lead to novel therapy to treat dermatitis by controlling leukocytes migration into cutaneous sites of inflammation.

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  Cyclosporin A and tacrolimus have been used as immunosuppressive agents initially in organ transplantation after their discovery, and are also used for treatment of the autoimmune disease, providing an excellent therapeutic effect. These agents act targeting on intracellular phosphatase calcineurin (CN), and subsequently inhibit activation of nuclear factor of activated T cells (NFAT), a key regulator of stimulation-dependent gene activation. The CN-NFAT system is involved not only in the immunoregulation including activation and development of helper T cells, regulatory T cells and NKT cells, but in a variety of cellular and developmental events other than immune system. CN inhibitors also affect organs outside of immune system leading to adverse effects, including nephrotoxicity and glucose intolerance. We review recent findings in CN-NFAT system, as well as development of potential CN inhibitors.

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  The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells.
  Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection.
  Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders.
  Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance.
  Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

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  22-year old woman who was previously diagnosed as having juvenile idiopathic arthritis (JIA) was treated with anti-TNF-α agents. Her disease activity was assessed as Stage IV and Class III by Steinbrocker's classification and resistant to steroids and methotrexate. Initially clinical findings responded well to infliximab (IFX), but polyarthritis recurred 15 months after the start of the treatment, and IFX was switched to etanercept (ETN) with good response. On the other hand, effects on the osteoarticular lesions were continuously observed through the period of the treatment with these two biologics. It was thought very rare that weight-bearing joint like the hip joint was restored as was seen in this case, while its mechanism is unknown. Because mechanism for inhibition of inflammation or joint destruction might be independent, we should investigate further the relationship between inflammation and joint destruction in the future.

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  The patient was a 64-year-old woman with a nearly 20-year history of sicca symptoms, having been given a diagnosis of primary Sjögren's syndrome. Three years previously, she experienced difficulty in walking up a slope and had leg malaise, which insidiously progressed to an inability to go up and down stairs. This disability brought her to our hospital, where her muscle strength was examined by manual muscle testing, and she was found to have reduced muscle strength in proximal muscles like the thigh muscles and the neck flexor muscles. Blood studies revealed elevated ESR, increased serum IgG, mildly increased myogenic enzymes, and positive results for anti-SS-A and -SS-B antibodies. MRI scans disclosed extensive muscle atrophy as well as fatty degeneration in the thigh. A biopsy of the quadriceps femoris muscle provided a diagnosis of myositis based on the finding of muscle fibers of unequal size, nuclear centralization, and inflammatory cell infiltration into muscle fibers. CD4-positive lymphocytes were the predominant inflammatory cells. We diagnosed the case as myositis in primary Sjögren's syndrome based on the clinical course and laboratory findings. She recovered well with steroid medication. It is noteworthy that myositis associated with primary Sjögren's syndrome presents with mild symptoms and unremarkable laboratory data but may run a chronic progressive course.

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  We report a case of reactive arthritis in a 21-year-old man who was successfully treated with methotrexate. In July 2008, the patient experienced arthritis in the left knee 3 days after being diagnosed as having urethritis by the urology clinic. The patient was treated with loxoprofen sodium and fosfomycin calcium at an orthopedic clinic. Antibiotics induced clinical improvement of urethritis, although arthritis became worse. Even after sulphasalazine and corticosteroid were started, polyarthritis remained persistent. Finally, methtrexate was added ; thereafter, polyarthritis and elevated CRP were resolved. HLA-B270502 was positive. Methotrexate could be one of the choices for sulphasalazine-resistant reactive arthritis.

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