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Review
. 2023 Mar 13:10:1158768.
doi: 10.3389/fmed.2023.1158768. eCollection 2023.

Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review

Gaetano La Rocca  1 , Francesco Ferro  1 , Chiara Baldini  1 , Alessandro Libra  2 , Domenico Sambataro  3 , Michele Colaci  4 , Lorenzo Malatino  4 , Stefano Palmucci  5 , Carlo Vancheri  2 , Gianluca Sambataro  2   3
Affiliations
Review

Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review

Gaetano La Rocca et al. Front Med (Lausanne). .

Abstract

In recent decades, several pieces of evidence have drawn greater attention to the topic of innate immunity, in particular, interferon (IFN) and Interleukin 6 in the pathogenesis of idiopathic inflammatory myopathies (IIM). Both of these molecules transduce their signal through a receptor coupled with Janus kinases (JAK)/signal transducer and activator of transcription proteins (STAT). In this review, we discuss the role of the JAK/STAT pathway in IIM, evaluate a possible therapeutic role for JAK inhibitors in this group of diseases, focusing on those with the strongest IFN signature (dermatomyositis and antisynthetase syndrome).

Keywords: 2; 3; Baricitinib; JAK/STAT 1; Tofacitinib; antisynthetase syndrome; dermatomyositis.

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Conflict of interest statement

CV is part of the F. Hoffmann-La Roche Ltd., Scientific Board. He has received consulting fees and/or speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini. GS and SP received honoraria from Boehringer Ingelheim outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Role of JAK in IIM. IFN receptors are coupled with JAK1 and 2, IFN α/β and IL6 also with TYK2. TGFβ is coupled with SMAD, however, it can also phosphorylate JAK and JAK2. The signal is transmitted to the nucleus through STAT, with a great role of STAT3. STAT1 is involved in inflammation, STAT2 in the promotion of apoptosis and STAT3 in the production of angiotensinogen. JAK, Janus kinases; IFN, interferon; IL, interleukin; SMAD, suppressor of mothers against decapentaplegic; STAT, signal transducer and activator of transcription proteins; TGF, transforming growth factor.
See this image and copyright information in PMC

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