# The Interleukin-7 Receptor Signaling Pathway and Its Perturbation in Immunodeficiency, Autoimmune Disease and Lymphoid Malignancy **Authors:** Alister C. Ward PMC · DOI: 10.3390/biom16020219 · Biomolecules · 2026-02-02 ## TL;DR This paper reviews how the IL-7 receptor signaling pathway influences immune cell development and its role in diseases like immunodeficiency, autoimmune disorders, and lymphoid malignancies. ## Contribution The paper offers a comprehensive overview of IL-7R biology and its mutations in immune diseases, highlighting therapeutic strategies. ## Key findings - IL-7R signaling is crucial for T-cell and B-cell development and immune homeostasis. - Mutations in IL-7R components are linked to immunodeficiencies, autoimmune diseases, and lymphoid malignancies. - Modulation of the IL-7R pathway is being explored as a therapeutic approach for immune-related disorders. ## Abstract Cell–cell signaling through a network of cytokine receptors is pivotal for normal immune development and function, with disruptions of these signaling pathways being implicated in a variety of immune cell diseases. Signaling via the interleukin-7 receptor (IL-7R) facilitates the development and homeostasis of various T-cell, B-cell and other immune-cell populations. This is reflected in the raft of mutants and variants of IL-7R components and downstream signaling molecules that have been identified in the context of immunodeficiencies, autoimmune disorders and lymphoid malignancies, but also through the use of pathway modulators as therapeutics. This review provides an overview of IL-7R biology, the role of mutations and variants affecting IL-7R signaling pathway components in the etiology of immune cell diseases and the specific therapies related to this pathway. ## Linked entities - **Proteins:** IL7R (interleukin 7 receptor) - **Diseases:** immunodeficiency (MONDO:0021094), autoimmune disease (MONDO:0007179) ## Full-text entities - **Genes:** STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, Wt1 (WT1 transcription factor) [NCBI Gene 22431] {aka D630046I19Rik, Wt-1}, ZEB2 (zinc finger E-box binding homeobox 2) [NCBI Gene 9839] {aka HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, RPL10 (ribosomal protein L10) [NCBI Gene 6134] {aka AUTSX5, DXS648, DXS648E, L10, MRXS35, NOV}, Hoxa9 (homeobox A9) [NCBI Gene 15405] {aka D6a9, Hox-1.7}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, SOCS1 (suppressor of cytokine signaling 1) [NCBI Gene 8651] {aka AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1}, Pprc1 (peroxisome proliferative activated receptor, gamma, coactivator-related 1) [NCBI Gene 226169] {aka A930018M19, PRC, mKIAA0595}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}, Nras (Nras proto-oncogene, GTPase) [NCBI Gene 18176] {aka N-ras}, DNM2 (dynamin 2) [NCBI Gene 1785] {aka CMT2M, CMTDI1, CMTDIB, DI-CMTB, DYN2, DYNII}, Ccl19 (C-C motif chemokine ligand 19) [NCBI Gene 24047] {aka CKb11, ELC, Gm2023, MIP3B, Scya19, exodus-3}, Nf1 (neurofibromin 1) [NCBI Gene 18015] {aka Dsk9, E030030H24Rik, Mhdadsk9, Nf-1}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, GFI1 (growth factor independent 1 transcriptional repressor) [NCBI Gene 2672] {aka GFI-1, GFI1A, SCN2, ZNF163}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, IL4R (interleukin 4 receptor) [NCBI Gene 3566] {aka CD124, IL-4RA, IL4RA}, Cd34 (CD34 antigen) [NCBI Gene 12490], IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, STAT5B (signal transducer and activator of transcription 5B) [NCBI Gene 6777] {aka GHISID2, STAT5}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Jak3 (Janus kinase 3) [NCBI Gene 16453] {aka fae, wil}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, Cdkn2a (cyclin dependent kinase inhibitor 2A) [NCBI Gene 12578] {aka ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IL9R (interleukin 9 receptor) [NCBI Gene 3581] {aka CD129, IL-9R}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, Phf6 (PHD finger protein 6) [NCBI Gene 70998] {aka 2700007B13Rik, 4931428F02Rik, mKIAA1823}, Notch1 (notch 1) [NCBI Gene 18128] {aka 9930111A19Rik, Mis6, N1, Tan1, lin-12}, CRLF2 (cytokine receptor like factor 2) [NCBI Gene 64109] {aka CRL2, CRLF2Y, TSLPR}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, Il7r (interleukin 7 receptor) [NCBI Gene 16197] {aka CD127, IL-7Ralpha}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, Ikzf1 (IKAROS family zinc finger 1) [NCBI Gene 22778] {aka 5832432G11Rik, Ikaros, LyF-1, Zfpn1a1, Znfn1a1, hlk-1}, EBF1 (EBF transcription factor 1) [NCBI Gene 1879] {aka COE1, EBF, O/E-1, OLF1}, CHDH (choline dehydrogenase) [NCBI Gene 55349], Jak1 (Janus kinase 1) [NCBI Gene 16451] {aka BAP004, C130039L05Rik}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, PIK3R2 (phosphoinositide-3-kinase regulatory subunit 2) [NCBI Gene 5296] {aka MPPH, MPPH1, P85B, p85, p85-BETA, p85beta}, Hoxa (homeobox A cluster) [NCBI Gene 111336] {aka Hox-1}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, IL2RG (interleukin 2 receptor subunit gamma) [NCBI Gene 3561] {aka CD132, CIDX, IL-2RG, IMD4, P64, SCIDX}, Myc (Myc proto-oncogene, bHLH transcription factor) [NCBI Gene 17869] {aka Myc2, Niard, Nird, bHLHe39}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Il7 (interleukin 7) [NCBI Gene 16196] {aka A630026I06Rik, Il-7, hlb368} - **Diseases:** respiratory tract infections (MESH:D012141), injury to (MESH:D014947), the disease (MESH:D004194), autoimmune arthritis (MESH:D001168), inflammation (MESH:D007249), prostate cancer (MESH:D011471), glioma (MESH:D005910), melanoma (MESH:D008545), RA (MESH:D001172), eczema (MESH:D004485), Immunodeficiency (MESH:D007153), leukemia (MESH:D007938), viral infections (MESH:D014777), growth defects (MESH:D006130), adult (MESH:C538052), steroid resistance (MESH:D009404), ETP-ALL (MESH:D054218), infections (MESH:D007239), ALL (MESH:D054198), X-linked form (MESH:C564041), lymphopenia (MESH:D008231), failure to thrive (MESH:D005183), Immune Cell Diseases (MESH:D007154), cancer (MESH:D009369), cytotoxicity (MESH:D064420), autism (MESH:D001321), meningitis (MESH:D008580), asthma (MESH:D001249), eosinophilia (MESH:D004802), immune cell cancers (MESH:D018295), Lymphoid Malignancies (MESH:D008223), B cell lymphoma (MESH:D016393), Autoimmune Disease (MESH:D001327), BCP (MESH:D015452), triple-negative breast cancer (MESH:D064726), autoimmune manifestations (MESH:D012877), T1D (MESH:D003922), diarrhea (MESH:D003967), hypersensitivity (MESH:D004342), pneumonia (MESH:D011014), autosomal recessive disorder (MESH:D030342), MS (MESH:D009103), erythroderma (MESH:D003873), Ph (MESH:D010677), Omenn's syndrome (MESH:D016511), ALLs (MESH:C536496), SLE (MESH:D008180), sepsis (MESH:D018805), infectious diseases (MESH:D003141) - **Chemicals:** NT-17 (-), temozolomide (MESH:D000077204), Tofacitinib (MESH:C479163), tyrosine (MESH:D014443), cysteine (MESH:D003545), Baricitinib (MESH:C000596027), Fedratinib (MESH:C528327), glucose (MESH:D005947), Ruxolitinib (MESH:C540383) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** R98S, S185C, Thr66Ile, A573V, rs6897932, rs766736182 ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12937949/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937949/full.md ## References 144 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937949/full.md --- Source: https://tomesphere.com/paper/PMC12937949