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• Two IL-2 paralogs (IL-2 and IL-2L) have been identified in sea bass. • IL-2 and IL-2L synteny and gene organization has been analyzed. • The molecular structure and expression analysis of these two paralogs has been studied. • The bioactivity of the sea bass IL-2 paralogs has been explored. • IL-2 and IL-2L are involved in fish T cell development and show a distinct biological role. In mammals, interleukin (IL)-2, initially known as a T-cell grow factor, is an immunomodulatory cytokine involved in the proliferation of T cells upon antigen activation. In bony fish, some IL-2 orthologs have been identified, but, recently, an additional IL-2like (IL-2L) gene has been found. In this paper, we report the presence of these two divergent IL-2 isoforms in sea bass (Dicentrarchus labrax L.). Genomic analyses revealed that they originated from a gene duplication event, as happened in most percomorphs. These two IL-2 paralogs show differences in the amino acid sequence and in the exon 4 size, and these features could be an indication that they bind preferentially to different specific IL-2 receptors. Sea bass IL-2 paralogs are highly expressed in gut and spleen, which are tissues and organs involved in fish T cell immune functions, and the two cytokines could be up-regulated by both PHA stimulation and vaccination with a bacterial vaccine, with IL-2L being more inducible. To investigate the functional activities of sea bass IL-2 and IL-2L we produced the corresponding recombinant molecules in E. coli and used them to in vitro stimulate HK and spleen leukocytes. IL-2L is able to up-regulate the expression of markers related to different T cell subsets (Th1, Th2 and Th17) and to Treg cells in HK, whereas it has little effect in spleen. IL-2 is not active on these markers in HK, but shows an effect on Th1 markers in spleen. Finally, the stimulation with recombinant IL-2 and IL-2L is also able to induce in vitro proliferation of HK- and spleen-derived leukocytes. In conclusion, we have demonstrated that sea bass possess two IL-2 paralogs that likely have an important role in regulating T cell development in this species and that show distinct bioactivities. [ABSTRACT FROM AUTHOR]

This review is focused on the pathogenesis of psoriatic arthritis (PSA) and the treatment. Furthermore, the paper underlined that the current therapeutic algorithms address the variety of clinical manifestations with a tailored strategy aiming to achieve the best control of the symptoms with minimal side effects. Finally, conventional immunosuppressive drugs, biologic agents and synthetic small molecules offer different attack routes and may be chosen individually or in combination according to the phenotype of the disease. The pathogenesis of psoriatic arthritis (PSA) is still a matter of debate. A favourable genetic background is interwoven with environmental triggering factors in a complex network. Shared antigens and the recirculation of immune cells may account for the clinical manifestations, involving both cutaneous and articular sites. A favourable genetic background has been demonstrated in many genomic and proteomic studies, being associated to polymorphic variants of the genes coding for Major Histocompatibility Complex I and cytokine pathways. In genetic-predisposed individuals, triggering factors, like infections, dysbiosis or mechanic stress may promote the development of the disease. The subsequent activation of the innate and adaptive immune system, following the stimulation of Toll-like Receptors, culminates in the expansion of dendritic cells, macrophages, CD4+ and CD8+ T cells, neutrophils, monocytes, Natural Killer lymphocytes and other cells with the final inflammation and damage of skin, joint and enthesis. Particularly, the activation of CD4+ T helper 17 lymphocytes represents a crucial point in the pathogenesis of the disease. The participation of the visceral adipose tissue may amplify the inflammatory process by means of the synthesis of pro-inflammatory adipokines. Current therapeutic algorithms address the variety of clinical manifestations with a tailored strategy aiming to achieve the best control of the symptoms with minimal side effects. Conventional immunosuppressive drugs, biologic agents and synthetic small molecules offer different attack routes and may be chosen individually or in combination according to the phenotype of the disease. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role of type I IFNs in regulating immune cell activation between wild-type and lupus-prone mice following UVB exposure. 10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 100 mJ/cm2 of UVB for 5 consecutive days. Following UVB treatment, draining lymph node cell populations were characterized via flow cytometry and suppression assays; treated skin was examined for changes in expression of type I IFN genes. Only NZM2328 mice showed an increase in T cell numbers and activation 2 weeks post UVB exposure. This was preceded by a significant increase in UVB-induced type I IFN expression in NZM2328 mice compared to BALB/c mice. Following UVB exposure, both BALB/c and iNZM mice demonstrated an increase in functional T regulatory (T Reg) cells; however, this was not seen in NZM2328 mice. These data suggest a skewed UVB-mediated T cell response in lupus-prone mice where activation of T cells is enhanced secondary to a type I IFN-dependent suppression of T Reg cells. Thus, we propose type I IFNs are important for UVB-induced inflammation in lupus-prone mice and may be an effective target for prevention of UVB-mediated flares. • Interferon responses to UVB are greater in lupus prone mice. • UVB induces T REG production to restrain T cell activation in wild type mice. • UVB induces T cell activation in lupus-prone mice secondary to inhibition of T REGs. • Type I IFN is required for T REG inhibition in lupus-prone mice. [ABSTRACT FROM AUTHOR]