title: TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.
abstract: In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1) has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL) and head kidney leukocytes (HKL). It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ) and T/B cell markers [Cd4-like (Cd4l), Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5), was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+) leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Mu
authors.initials: M
authors.lastname: Yang
authors.forename: Xinyan
authors.initials: X
authors.lastname: Wang
authors.forename: Danyan
authors.initials: D
authors.lastname: Chen
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.forename: Anying
authors.initials: A
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000918:Antibody Specificity; D002347:Carps / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I