Chemokines are a large family of soluble peptides guiding cell migration in development and immune defense. They regulate immune cell migration, both under inflammatory and normal physiological conditions through their cognate receptors, acting as a bridge between innate and adaptive immunity. Notably, members of the CXCL chemokine family and their receptors are heavily involved in the spatial organization of the adaptive immune system and are believed to have evolved from a common origin.

Immunoevolution studies suggest that multiple CXCL chemokines diverged in jawless fish with a common origin in agnanthans (jawless fish) and gnathostomes (jawed vertebrates). The adaptive immune system arose in vertebrates with lymphocytes and immunoglobulins (Igs) crucial for human and all gnathostome (jawed vertebrate) immunity. In 1970, the joining (J) chain was discovered as a critical protein regulating the pentamerization of IgM and dimerization of IgA via disulfide bonding between J chain and Ig secretory tail. Despite the commonalities in CXCL chemokine and J chain evolution, the primordial relationships, if any, between chemokines and the adaptive immune system remain little understood.

Recent work by Flajnik and colleagues in the Department of Anthropology at Pennsylvania State University and the Department of Microbiology and Immunology at the University of Maryland have discovered shared ancestral characteristics between the exon-intron structure of the JCHAIN genes and CXCL chemokines. Interestingly, the JCHAIN and CXCL genes share a four-exon structure, with conserved intron phases between those exons. Exons 1 and 3 of CXCL and JCHAIN are of comparable size, with conserved Cys-Amino Acid (X)-Cys motifs canonical for CXCL genes present in exon 2 of JCHAIN (figure). Analysis of multiple jawed vertebrates suggest that JCHAIN arose from conserved synteny, i.e. conserved sequence of aligned genes between species, and gene structure from CXCL chemokines. These data suggest the potential co-evolution of a subset of the larger chemokine family coincident with the adaptive immune system in vertebrate animals.

Checkout out the full line of CXCL family of chemokines at Protein Foundry.

Proc Natl Acad Sci U S A. The immunoglobulin J chain is an evolutionarily co-opted chemokine [PNAS 2024 Jan 16;121(3):e2318995121. doi: 10.1073/pnas.2318995121]