New Insights into the Mechanisms of Innate Immune Receptor Signalling in Fibrosis



Robert Lafyatis*, Alessandra Farina
Rheumatology Section, Boston University School of Medicine, Boston, MA, USA


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© Lafyatis and Farina; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Boston University School of Medicine, 88 E Concord St, Boston, MA 02118, USA; Tel: 617 638-4312; Fax: 617 638-5226; E-mail: lafyatis@bu.edu


Abstract

Recent advances in our understanding of innate immunity and inflammation have direct bearing on how we understand autoimmunity, and fibrosis, and how innate immune sensors might stimulate both of these key features of several fibrotic diseases. Toll-like receptors (TLRs) are the major receptors for recognizing pathogen associated molecular patterns present on bacterial cell walls, such as LPS, and nucleic acids (RNA and DNA). Several intracellular pathways mediate TLR effects and initiate various pro-inflammatory programs. Mechanisms for control of inflammation, matrix remodeling, and ultimately fibrosis are also activated. Transforming growth factor-beta (TGF-β), Interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-13 (IL-13), and interferon (IFNs) appear particularly important in regulating pro-fibrotic aspects of innate immune activation. These mechanisms appear important in fibrotic disease affecting multiple organ-systems, including lung, liver, kidney, and skin. These observations provide new paradigms for understanding the relationship between immunity/inflammation and fibrosis, however, the precise ligand and mechanism linking innate immune sensor(s) to fibrosis remain uncertain in most illnesses.

Keywords: Scleroderma, toll-like receptors, Rig-I-like receptors, Nod-like receptors, fibrosis..