February 2022

Terapias alvo e Janus quinases em reumatologia: um enfoque baseado nos mecanismos

Nat Rev Rheumatol. 2022 Jan 5:1–13. Epub ahead of print doi: 10.1038/s41584-021-00726-8

The development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders, to the extent that they could ultimately enable either complete withdrawal or avoidance of glucocorticoid use in some autoimmune diseases, and could have the potential to regulate any active factor inhibiting the transition to cure.In this review paper, Tanaka, et al. describe the progress in JAK-targetin...

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April 2015

Super-enhancers delineate disease-associated regulatory nodes in T cells

Nature. 2015 Feb 16. doi: 10.1038/nature14154. [Epub ahead of print]

Transcription machinery (proteins responsible for activating or ‘switching off’ genes) is not distributed in the genome in a symmetrical (or even) manner. Some parts of the genome, so called super-enhancers (SEs), accumulate an exceptionally high level of proteins relevant to the regulation of transcription (i.e. the machinery is concentrated in particular parts of the genome). In this paper, the investigators asked about the locale of these regions in the genome of T cells. Then they addressed...

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June 2013

Janus kinases in immune cell signaling

Immunological Reviews 2009; 228:273-87

This review from 2009 describes the Janus Kinases (JAK) that includes JAK1, JAK2, and JAK3, a subgroup of non-receptor protein tyrosine kinases. This protein family has a diverse range of functions including roles in cell growth, survival, development, and differentiation of a variety of cells, and especially immune and haematopoietic cells. Current knowledge of protein structure, regulatory mechanisms, signalling pathways and intracellular interactions for the JAK family is reviewed. The paper ...

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Back to the future: oral targeted therapy for RA and other autoimmune diseases

Nature Reviews Rheumatology 2013; 9(3):173-82

This review paper considers how advances in understanding of the disease process underlying rheumatoid arthritis (RA) and the development of novel techniques have transformed the management of this progressively disabling condition. Physicians are no longer limited to prescribing symptomatic treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) or choosing from a seemingly random array of drugs drawn from multiple disciplines, such as methotrexate and sulphasalazine, which are descri...

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Janus kinases inhibitors in autoimmune diseases

Annals of the Rheumatic Diseases 2013; 72:ii111-ii115

This review describes the role of various cytokines in rheumatoid arthritis (RA) and related diseases. This includes an overview of the different types of cytokine receptors including type I, which bind some of the interleukins (ILs), colony stimulating factors (CSFs) and hormones such as erythropoietin, prolactin and growth hormone (GH); and type II, which bind to interferons and IL-10-related proteins. In addition, the cytoplasmic domain of type I and II cytokine receptors bind to members of a...

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