Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

IL-1R8 Downregulation and Concomitant TLR7 and TLR9 Up-Regulation Are Related to the Pathogenesis of Canine Diffuse Large B-Cell Lymphoma

Federica Riva
ORCID logo ,
Joel Filipe
ORCID logo ,
Antonella Fanelli
,
Laura Marconato
ORCID logo ,
Alessia Inglesi
ORCID logo ,
Eugenio Scanziani
,
Sabina Soldati
,
Luca Licenziato
,
Stefano Comazzi
ORCID logo ,
Lucia Minoli
* ORCID logo ,
Luca Aresu
ORCID logo
Version 1 : Received: 8 April 2022 / Approved: 11 April 2022 / Online: 11 April 2022 (09:15:27 CEST)

A peer-reviewed article of this Preprint also exists.

Riva, F.; Filipe, J.; Fanelli, A.; Marconato, L.; Inglesi, A.; Scanziani, E.; Soldati, S.; Licenziato, L.; Comazzi, S.; Minoli, L.; Aresu, L. IL-1R8 Downregulation and Concomitant TLR7 and TLR9 Upregulation Are Related to the Pathogenesis of Canine Diffuse Large B-Cell Lymphoma. Vet. Sci. 2022, 9, 209. Riva, F.; Filipe, J.; Fanelli, A.; Marconato, L.; Inglesi, A.; Scanziani, E.; Soldati, S.; Licenziato, L.; Comazzi, S.; Minoli, L.; Aresu, L. IL-1R8 Downregulation and Concomitant TLR7 and TLR9 Upregulation Are Related to the Pathogenesis of Canine Diffuse Large B-Cell Lymphoma. Vet. Sci. 2022, 9, 209.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common haematological malignancy in humans and dogs. Several studies disclosed some similarities between the two species, including the constitutive activation of NF- κB pathway as a fundamental underlying pathogenetic mecha-nism. In humans, downregulation of IL-1R8 is implicated in DLBCL development, but its role in dogs has not been explored so far. To gain insight into the pathogenesis of this tumor in dogs, we evaluated the mRNA and protein expression of IL-1R8 in 12 hyperplastic lymph nodes ob-tained from dogs not bearing tumors and from 50 dogs with DLBCL. Moreover, we analysed through qRT-PCR the expression of TLR7, TLR9, MYC, and p52 genes that are known to be in-volved in the IL-1R8 regulatory network. IL-1R8 and p52 were downregulated in DLBCLs com-pared to control lymph nodes (p<0.001), while a higher expression of TLR7, TLR9 and MYC was observed in tumors (p<0.01). Immunohistochemistry confirmed gene expression results, reveal-ing a significantly lower IL-1R8 staining score in DLBCLs compared to control lymph nodes (p<0.0001). Taken together, these results suggest that IL-1R8 downregulation may represent one of the mechanisms driving DLBCL pathogenesis in dogs, mainly through dysregulation of the Toll-like/Interleukin receptors signalling cascade and the aberrant activation of classical NF-κB pathway.

Keywords

dog; diffuse large B-cell lymphoma; IL-1R8; TLR7; TLR9; qRT-PCR

Subject

Medicine and Pharmacology, Veterinary Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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