Publication:
African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates

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Date
2015-09-21
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Authors
Tacchi, Luca ; Larragoite, Erin T. ; Muñoz, Pilar ; Amemiya, Chris T. ; Salinas, Irene
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Publisher
Elsevier
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DOI
http://dx.doi.org/10.1016/j.cub.2015.07.066
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Description
©2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published, version of a Published Work that appeared in final form in Current Biology. To access the final edited and published work see http://dx.doi.org/10.1016/j.cub.2015.07.066
Abstract
One of the most remarkable innovations of the verte brate adaptive immune system is the progressive orga nization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tis sues (O-MALT) such as Peyer’s patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates(LAs) were found in themucosa of anuran amphibians [1], suggesting that O-MALT evolved from amphibian LAs 250 million years ago [1–4]. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representa tive of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associ ated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infec tion, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses re vealed its extraordinary diversification within sarcop terygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs.
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