Antigen-specific CD4⁺ helper T cell (Th cell) is a major player for acquired-immunity. Th cell distribute in the peripheral tissues after educations and selections in the thymus. By stimulation from antigen presenting cell (APC), Th cell differentiate into at least three types of effector Th cells by the cytokine environments and the kinds of co-stimulatory molecules on APC. One is Th1 cell which produces IFN-γ mainly, and another is Th2 cell which produces IL-4, 5 and 13 mainly, and finally recently defined Th17 cell which produces IL-17 mainly, and these cells are charged with the a role for “cellular”, “hormoral” and “inflammatory” immunity respectively. IL-12, STAT4 and T-bet signals are important for Th1 differentiation, and IL-4, STAT6 andGATA3 signals are important for Th2 differentiation, and IL-1β, TGF-β, IL-6, IL-23, STAT3, RORγt signals are important for Th17 differentiation. This newly defined Th17 cell clearly makes a big progress for understanding the pathophysiology of many inflammatory conditions. In the near future, many biologics or compounds that regulate the production or function of IL-17 will be produced aggressively.

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  Macrophage activation syndrome (MAS) is a rare and potentially lethal disease, resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. Adult-onset Still's disease (AOSD) is an inflammatory disease. AOSD resemble reactive MAS in its symptoms and laboratory data. Moreover, AOSD per se induces MAS. It is, therefore, quite difficult to differentiate these syndrome and disease. The immunodeficiency state induced by treatment in AOSD could reactivate latent viruses such as Epstein-Barr virus, which could potentially lead to MAS. The therapeutic agents for AOSD, such as sulfasalazine, also could provoke reactive MAS. Because multiple factors are involved in inducing MAS to a different degree, the main cause should be searched for and targeted for the therapy.

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  Since antineutrophil cytoplasmic autoantibody (ANCA) was found, the researches in the pathogenesis of vasculitis syndrome have been developing. Proinflammatory cytokines including tumor necrosis factor-α are induced by certain infections, by which ANCA that binds to granule components of cytoplasm adhesions to endothelial cells. These endothelial cells produce proteolytic enzymes and oxygen radicals, which leads to vasculitis. It might be contributed in the production of ANCA that bacterial organisms are mimicry to the peptide sequences of granule components. The multicentric randomized clinical trials undertaken by the European Vasculitis Study Group (EUVAS) optimized that cyclophosphamide-corticosteroid combination therapy was useful to ANCA-associated vasculitis. It is increasing evidences that biologics are useful to ANCA-associated vasculitis, although it is necessary to take care of severe adverse effects.

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  The inflammatory muscle diseases, polymyositis (PM) and dermatomyositis (DM) are systemic connective tissue disorders characterized by chronic inflammation in skeletal muscle and involvement of various systemic organs. The pathogenesis of these heterogeneous diseases is unknown, but appear to mediate an autoimmune disorder that culminates in the tissue damage. Autoantibodies directed against various cellular constituents have been detected in patients with PM/DM, and 40-50% of patients have autoantibodies (myositis-specific antibodies : MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with characteristic clinical features and therefore provide us useful information for diagnosis, patient classification as well as predict of signs, symptoms of myositis, response to treatment, and prognosis.
  Autoantibodies to the cytoplasmic antigens, that are involved in protein synthesis or translation related proteins, are seen in patients with PM. Autoantibodies to eight of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an “anti-synthetase syndrome.” However, certain differences of the clinical features associated with each anti-synthetase have been noted, although their similarity is impressive. Anti-signal recognition particle antibodies are associated with severe, refractory myositis that differs significantly from anti-synthetase syndrome. Autoantibodies to the nuclear antigen, Mi-2 that is a transcription-regulating protein, are specifically seen in patients with DM responsive to corticosteroid therapy.
  In recent years, novel MSAs have been identified in clinically amyopathic dermatomyositis (anti-CADM-140 antibodies) and malignancy-associated myositis (anti-p155 and p155/p140 antibodies), in which autoantibodies have been thought to be negative. For understanding the pathogenic mechanisms of PM/DM, it is important to elucidate the relationship between these novel MSAs and their related clinical entities.
  Recently the nature of the target MSA autoantigens has been characterized using molecular biology and proteomic techniques. However, the mechanism of development of MSAs remains unknown. Further analysis of the molecular structure and biological function of target autoantigens recognized by these MSAs might provide the clues to the understanding of the etiology and pathogenesis of these disorders.

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  Stem cell therapy is expected to be a promising approach for the compensation of lost organs. The various organization cells that compose an animal's body are always being renewed for the maintenance of homeostasis. The cells that become the source of new cells are a body's own stem cells. Cell therapy, using stem cells, has a few of bioethical problems but there is the advantage that it is not necessary to worry about the immunity rejection of the transplant because the body's stem cell is from it's own body. In our present study we identified side population cells (SP cells), which are highly enriched for stem cell activity in human salivary glands. Isolated SP cells expressed high level of DNp63 and PSCA (prostate stem cell antigen), but not nestin, Oct4 and CD34. Real time PCR analysis revealed that the expression of DNp63, detected in immature salivary epithelial cells, gradually decreased through cell differentiation. In contrast, PSCA can be distinguished among early differentiating and later transit-amplifying salivary epithelial cells in tissue culture. Our study suggested that these markers may mark the transition of human salivary epithelial cells.

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  A 69-year-old male was diagnosed with rheumatoid arthritis(RA) in 1994. Good control of the RA activity had been obtained with sodium aurothiomalate (GST). However, polyarthritis reappeared in January 2003. He was examined at the Division of Rheumatology, Department of Internal Medicine, Saitama Social Insurance Hospital in August 2003. The treatment was switched from GST to salazosulfapyridine (SASP), with improvement of the polyarthritis. Subsequently, in March 2005, the patient developed fever, pancytopenia and liver dysfunction, and was admitted to Saitama Social Insurance Hospital. Since these abnormalities were suspected to be caused by SASP, this drug was stopped and prednisolone (PSL) was started at 10 mg/day. However, since the fever, pancytopenia and liver dysfunction persisted, bone marrow examination was performed and the patient was diagnosed with acute lymphoblastic leukemia (pre B cell type, L2). He was transferred to the Division of Hematology, Omiya Medical Center, Jichi Medical University, on 8^th April, 2005 for induction chemotherapy. Although the induction therapy needed to be stopped because the patient developed dysphagia and biliary system dysfunction, complete remission (CR) was confirmed. It was difficult to restart chemotherapy in the patient because his general condition remained poor, with repeated episodes of aspiration pneumonia and newly detected stomach cancer. He was, therefore, transferred back to Saitama Social Insurance Hospital on 28^th September, 2005. The ALL remained in CR and the RA activity had disappeared without therapy, but the patient died of pneumonia on 1^st August, 2006.

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