Semaphorins are soluble and membrane-bound proteins originally identified as axonal growth cone-collapsing guidance molecules which are involved in the development of the neuronal system. Recently, cumulative evidences indicate that several semaphorins also participate in various phases of immune responses, both physiological and pathological. They are so-called ‘immune semaphorins’ such as sema3A, 3E, 4A, 4D, 6D, and 7A. Some semaphorins regulate immune cell activation or differentiation, whereas others navigate the trafficking of immune cells. Moreover, Plexin family members and neuropilins are the most representative receptors for semaphorins, which have cell type-specific patterns of expression and are involved in multiple signaling responses. At present, semaphorins and their receptors are considered to be potential diagnostic and therapeutic targets for many kinds of diseases. Here, we review the current knowledge of the function of semaphorins and their corresponding receptors in immune systems, which is especially focused on class3 and class4 semaphrins.

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  Recently, autoimmune pancreatitis (AIP) has been classified into two subtypes: type 1 as a pancreatic manifestation of IgG4-related disease (IgG4-RD), and type 2 related with a granulocytic epithelial lesion (GEL). Different from type 2 AIP, T helper type 2 (Th2) immune response is predominant over Th1 in type1/IgG4-RD. Recent human and experimental animal studies have suggested a possible involvement of innate immunity in addition to acquired immunity, such as genetic background, bacterial/viral infections, complement activation via classical pathway, or IgG4-production of monocytes/basophils with TLR/NOD stimulation. Based on these findings, we have proposed a hypothesis for the development of type1 AIP, one of the IgG4-RD.

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  Mucosal associated invariant T (MAIT) cells express a semi-invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. They are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and cells are selected in the thymus. Interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. MAIT cells display antimicrobial capacity. Recently, vitamin metabolites were demonstrated as antigens created by intestinal flora for MAIT cells. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), wheras they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

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  It has been reported that the exacerbation or development of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis may have seasonality, although the seasonal characteristic depends on each disease. For example, the sunlight (ultraviolet) and infectious pathogens are involved in important environmental factors contributing the seasonality of the diseases. Furthermore, recent advances include the association between vitamin D and autoimmune diseases, and the different pathogenesis among the same clinical category according to the autoantibodies.

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  Pseudomonas aeruginosa is an indigenous bacteria which inhabits on the surfaces of aqueous environments and is representative pathogen that causes opportunistic infection. P.aeruginosa is classified as low-virulence organism because it rarely causes infection in immunocompetent hosts, but in immnocompromised hosts it can cause a variety of severe infections leading to mortality. P.aeruginosa is also a representative pathogen of nosocomial infection. Emerging multidrug-resistant P.aeruginosa is now causing serious problems on clinical site. Regarding virulence factors, increasing number of studies using gene disrupted mutant bacterial strains revealed that P.aeruginosa possesses a variety of machinaries such as type 3 secretion system, exoenzyme, biofilm formation that impairs or evades host immune system. Also it is getting clarified that the virulence of P.aeruginosa is controlled by an inter-bacterial signal transduction system called quorum sensing. Meanwhile, studies on the host defense system using various gene targeting mice revealed the mechanisms by which host immune system detects and defends against invasion of P.aeruginosa. In this review, we describe these virulence factors, the mechanisms impairing host immune system, host's pathogen recognition system and immune evasion by P.aeruginosa.

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  Allogeneic Hematopoietic stem cell transplantation (allo-HSCT) is effective for several diseases, including leukemia, solid tumors, and immunodeficiency. However, there are still some intractable diseases that cannot be treated with HSCT alone. We have developed a new HSCT method, allo-HSCT + thymus transplantation (TT) from the same donor, which induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (HSCT + DLI). This method leads to improvement of immune function and the ability of engraftment, and is effective for treatment of autoimmune chronic pancreatitis and sialoadenitis in aging, lupus nephritis in hosts with radioresistance, and supralethal irradiation, in which conventional HSCT alone is ineffective. This method may become a valuable form of clinical therapy for intractable diseases.

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  In the present study, we assessed the relationship between polymyalgia rheumatica (PMR) and matrix metalloproteinase-3 (MMP-3) levels during the first medical examination and during treatment. We examined 22 patients with PMR in our hospital from 2010 to 2012, in whom the diagnosis was confirmed by the 2012 Provisional Classification Criteria for PMR. The MMP-3 levels were obtained from 19 patients, and the average MMP-3 level was 200.8 ng/mL; this level increased in 15 patients. During the 1 month after treatment initiation, the average dose of prednisolones (PSL) was increased from 2.75 mg/day to 11.3 mg/day, whereas the C-reactive protein level decreased from 6.92 mg/dL to 0.33 mg/dL; however, the average MMP-3 levels increased to 225.1 ng/mL during this period. When comparing the 7 patients in whom PSL withdrawal was achieved within 1 year and the patients in whom PSL withdrawal was difficult, we noted that the MMP-3 levels were higher in the patients in whom PSL withdrawal was difficult, and the MMP-3 level at 3 months after the first medical examination was significantly higher compared to the MMP-3 level during the first medical examination (p = 0.011). Although the MMP-3 level is influenced by PSL use, the MMP-3 levels may be considered to reflect the disease activity of PMR. Thus, MMP-3 levels may be a useful predictive factor for the success of PSL withdrawal in patients with PMR.

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  We describe a previously healthy 9-year-old girl who had multiple purpura several days after acute adenovirus gastroenteritis and mycoplasma pneumonia. Initial laboratory evaluation revealed a prolonged prothrombin time (PT) and APTT, low complement levels (C4, CH50), and positive immune complex (C1q) in her serum. Platelet count, fibrinogen, and other routine blood chemistry tests were normal. The prolonged APTT was not corrected by mixture of the patient's plus normal plasma. Clotting activities of factors II, V, VIII, IX, X, XI, and XII reduced. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT), and anticardiolipin antibodies. Mycoplasma pneumonia was treated by minocycline and the patient's skin lesions disappeared spontaneously within a week. During follow-up, she showed no other bleeding symptoms, and no signs of SLE or other autoimmune diseases. Four weeks after admission to our hospital, blood coagulation tests and serum complements normalized. Clotting activities of factors and antiphospholipid antibodies were not detected, half year later. The bleeding in this case was associated with acquired hypoprothrombinemia caused by antiphospholipid antibodies following acute adenovirus gastroenteritis and mycoplasma pneumonia.

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  A 35-year-old man had a 2-year history of uveitis and arterial wall thickening of an aortic branching artery detected by magnetic resonance imaging. He was admitted to our hospital because of mental exaltation. He had been treated with a moderate dose of prednisolone (30 mg/ml) plus methotrexate (6 mg/week) under the diagnosis of Takayasu arteritis for 2 years. Neurological examinations and brain magnetic resonance imaging taken on admission showed no abnormal findings. Although cerebrospinal fluid showed four cells/mm3 and 45 mg/dl of protein, cerebrospinal fluid interleukin-6 levels were markedly elevated (65.4 pg/mL), suggesting the neuro-Behçet's disease. The diagnosis of coexistence of vasculo- and neuro-Behçet's disease was made because vascular lesions are considered as a complication of Behçet's disease. We performed DNA testing using direct sequencing of all exons of the MEFV gene because of the patient's history of periodic fever since 30 year-old. The E148Q/L110P compound heterozygous mutation was found. His neurological symptoms and periodic fever were well controlled after the administration of infliximab (5 mg/kg every 2-month interval). Although occurrence by chance cannot be ruled out, the unusual findings of this patient suggest that MEFV mutations have some etiopathogenic mechanisms of an atypical phenotype of Behçet's disease.

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