cKit Ligand (Stem Cell Factor)-Induced Immune Response via an Alternative Receptor in Human Cells

Jihyung Hwang; Angela Reinert; Arthur Stem; Saerok Shim; Sinae Kim; HeeJoon Kim; Myungdal Yoon; Seungheon Lee; Donghwan Song; Hyun Yoo; Sunyoung Han; Mijeong Choi; Jared M. Brown; Soohyun Kim

doi:10.53941/jiim.2025.100005

Abstract

cKit (also known as CD117) is known for stem cell factor (SCF) receptor and it is involved in bone marrow hematopoietic stem cell (HSC) proliferation as well as mast cell growth. We have cloned the cDNA of cKit ligand (cKit-L; also known as SCF) from human keratinocyte HaCaT cells. Recombinant HaCaT cKit-L protein was produced and characterized whether it is active on HMC-1 cell expressing very high level of cKit transcript. Interestingly, HMC-1 cells did not respond to its ligand HaCaT cKit-L, whereas the same recombinant HaCaT cKit-L induced inflammatory chemokine interleukin 8 (IL-8) in human THP-1 monocyte cells that do not express cKit (also known as CD117). We wonder if HMC-1 is defective in the production of inflammatory molecules. Nevertheless, HMC-1 cells produce significant amounts of human IL-8 in response to IL-1a and IL-33. Commercial cKit-L was used to confirm these results, and the activity of commercial cKit-L was very similar to that of HaCaT cKit-L. These data suggest that the known cKit-L receptor cKit is required for cKit-L activity but is not sufficient to complete the immunological activity of cKit-L. It is possible that alternative cKit-L receptors exist that are responsible for inducing IL-8 in human and mouse immune cells.

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