Abstract
Tumor necrosis factor (TNF)-like weak inducer of apoptosis or TWEAK is a member of the TNF superfamily involved in the regulation of many biological processes. In mammals, TWEAK has been shown to play a role in some autoimmune or inflammatory conditions, but its immune role is not yet clearly defined. In teleost fish, although a few studies have identified homologues to mammalian TWEAK, their biological effects have never been investigated. In the current study, we have studied the transcriptional regulation of two TWEAK homologues (TWEAK 1 and 2) identified in rainbow trout (Oncorhynchus mykiss) throughout different tissues, in response to parasitic or viral infections, or in head kidney (HK) leukocytes stimulated with different stimuli. Although the transcription of both homologues was modulated when HK leukocytes were exposed to several immune stimuli, only TWEAK 1 was significantly modulated upon pathogenic exposure. Thus, we performed a characterization of the functions exerted by this cytokine in HK leukocytes. Recombinant TWEAK 1 strongly up-regulated the transcription of pro-inflammatory genes and antimicrobial peptides in HK leukocytes, with differential transcriptional effects in IgM+ B cells, IgM- lymphocytes and myeloid cells. TWEAK 1 also increased the survival and promoted the differentiation of B cells in HK leukocyte cultures. Our results demonstrate that in teleost fish, TWEAK 1 is involved in the response to different types of pathogens, through the modulation of antimicrobial and pro-inflammatory genes in different leukocytes subsets. Furthermore, a role for TWEAK as a B cell differentiation factor has also been established in rainbow trout.
Highlights
In mammals, the tumor necrosis factor superfamily (TNFSF) of cytokines activates signaling pathways that are involved in different cellular activities such as organogenesis, survival, apoptosis, inflammation, lymphocyte homeostasis, or cellular differentiation [1]
We studied the transcription of TNF-like weak inducer of apoptosis (TWEAK) 1 and 2 in response to different pathogenic experiences, that is fish affected by proliferative kidney disease (PKD), a disease caused by the myxozoan parasite Tetracapsuloides bryosalmonae and fish infected with viral hemorrhagic septicemia virus (VHSV)
TWEAK is an important member of the Tumor necrosis factor (TNF) superfamily that exerts a wide range of immune actions and seems to contribute to the pathogenesis of several diseases
Summary
The tumor necrosis factor superfamily (TNFSF) of cytokines activates signaling pathways that are involved in different cellular activities such as organogenesis, survival, apoptosis, inflammation, lymphocyte homeostasis, or cellular differentiation [1]. There are 19 known TNFSF ligands described in human and mouse [2]. These ligands are type II membrane-bound proteins. The TNF-like weak inducer of apoptosis (TWEAK) is one of these ligands (TNFSF12) and can be found as a homotrimeric type II transmembrane protein or as a soluble protein released by furin proteases [3]. Both forms can be expressed simultaneously but the mechanisms that control their relative production are still not known. The TWEAK-Fn14 pathway has recently been associated with the pathogenesis of several autoimmune disorders including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS) [7, 8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
