CD127 is the alpha subunit of the interleukin-7 receptor (IL-7Rα). It also functions as a receptor for thymic stromal lymphopoietin (TSLP). CD127 regulates the proliferation, differentiation, and survival of immune cells, particularly lymphocyte development. Loss-of-function mutations and certain polymorphisms of IL7Rα are associated with immunodeficiency and inflammatory diseases, respectively.

CD127 composition and distribution

CD127 exists in two forms: membrane-bound IL-7Rα and soluble IL-7Rα (sIL-7Rα), with distinct biological functions. sIL-7Rα competes with membrane IL-7R, reducing excessive IL-7 consumption and antagonizing IL-7 signaling, thereby enhancing IL-7 bioactivity when cytokine availability is limited. Furthermore, sIL-7R directly binds to membrane-bound IL-2Rγ and inhibits IL-7 signaling in IL-2Rγ-positive cells. Membrane-bound IL-7Rα promotes cell growth and proliferation and inhibits apoptosis by regulating the IL-7 signaling pathway.

CD127 is primarily found on T cells, B cells, and NK cells, as well as DCs, innate lymphoid cells (ILCs), and lymphoid tissue induction (Lti) cells. CD127 is also expressed in some solid tumors, including breast cancer, melanoma, leukemia, lung cancer, and cutaneous T-cell lymphoma.

(Data source: uniprot)

CD127 structure:

CD127 is a transmembrane protein. The human IL-7Rα gene is located on chromosome 5. CD127 has a molecular weight of approximately 49.5 kDa and is composed of an N-terminal extracellular region, a transmembrane domain, and a C-terminal intracellular region. The extracellular domain of CD127 consists of two fibronectin type III (FNIII) domains, D1 and D2, on which specific amino acids are responsible for binding to IL-7.

(Data source: Marković I, et al. Front Immunol. 2020)

CD127 signaling pathway and regulation:

The function of IL-7 is mediated by the IL-7R, a heterodimer composed of the IL-7R α chain (CD127) and the common γ chain (IL-2Rγ). Upon binding of IL-7 to IL-7Rα, the α and γ chains dimerize. IL-7 induces activation of kinases in the IL-7R downstream signaling pathway, including JAK1 (bound to IL-7Rα) and JAK3 (bound to the common γ chain), STAT1, STAT3, STAT5, PI3K, AKT, and MAPK. IL-7 signaling promotes cell proliferation and survival and inhibits apoptosis by regulating nuclear gene expression levels, including a decrease in pro-apoptotic factors (such as Bad and Bax) and cell cycle inhibitors (p21 CIP1 and p27 KIP1) and an increase in anti-apoptotic factors (such as Bcl-XL, Bcl-2, McL-1) and glucose metabolism regulators (Glut1, HXKⅡ). 

(Data source: Huang J, et al. Front Immunol. 2021)

Clinical value of CD127

Disease Detection: In certain disease states, such as acute lymphoblastic leukemia (ALL), CD127 expression levels may correlate with disease progression and response to treatment.

As a therapeutic target: Lusvertikimab (formerly known as OSE-127), an IgG4 antibody targeting IL-7Rα (CD127), is a full antagonist of the IL-7R pathway. Lusvertikimab targets ALL cells through a dual mode of action, including direct IL-7R antagonism and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP).

(Data source: Lenk L, Baccelli I, Laqua A, et al. Blood. 2024)

CAR-T cell therapy: In CAR-T cell therapy, the expression of CD127 may affect the persistence and anti-tumor effect of CAR-T cells.