Role of chemokine-like factor 1 as an inflammatory marker in diseases

Abstract

Immunoinflammatory mechanisms have been incrementally found to be involved in the pathogenesis of multiple diseases, with chemokines being the main drivers of immune cell infiltration in the inflammatory response. Chemokine-like factor 1 (CKLF1), a novel chemokine, is highly expressed in the human peripheral blood leukocytes and exerts broad-spectrum chemotactic and pro-proliferative effects by activating multiple downstream signaling pathways upon binding to its functional receptors. Furthermore, the relationship between CKLF1 overexpression and various systemic diseases has been demonstrated in both in vivo and in vitro experiments. In this context, it is promising that clarifying the downstream mechanism of CKLF1 and identifying its upstream regulatory sites can yield new strategies for targeted therapeutics of immunoinflammatory diseases.

Keywords: chemokine-like factor 1; immune-related disease; pathogenic mechanism; signaling pathways; targeted therapy.

Figure 1

CKLF1 binds to CCR4 and activates the NF-κB classical pathway, causing a variety of biological processes, including the release of inflammatory factors in the nucleus, the transcription of anti-apoptotic genes, and the expression of mitogenic proteins, which are involved in the regulation of immune-inflammatory responses.

Figure 2

CKLF1 mediates cell proliferation, differentiation, and apoptosis by binding to CCR4 and activating the MAPK signaling pathway to induce intranuclear gene transcription.

Figure 3

CKLF1 binds to CCR4 and induces the cell cycle regulatory gene expression through the IL-6/JAK/STAT3 signaling pathway, which is involved in tumor development.

Figure 4

CKLF1 binds to both CCR4 and CCR5 and activates the PI3K/AKT signaling pathway, which plays a role in inflammatory injury through diverse downstream substrates of AKT and mTORC1.

Figure 5

CKLF1 binds to CCR4 and induces the release of stored Ca2+ through the PYK2 pathway, activates autophosphorylation at the PYK2-tyr402 site, and regulates the migration of SH-SY5Y cells.

Figure 6

CKLF1 binds to CCR4 and mediates the activation of downstream NLRP3 inflammasomes. Activated caspase-1 induces maturation and release of pro-inflammatory cytokines and exacerbates inflammatory injury.

Figure 7

Signaling crosstalk across downstream pathways of CKLF1.