IL4是一種細胞因子，主要由T細胞和嗜堿性粒細胞產(chǎn)生。它在免疫反應中發(fā)揮重要作用，如調(diào)節(jié)B細胞的增殖和分化，增強抗體的產(chǎn)生等。最近的研究表明，IL4在某些腫瘤的免疫治療中具有重要作用。例如，IL4可以增強CAR-T細胞對癌細胞的殺傷作用，并且可以通過改變腫瘤微環(huán)境中的免疫細胞和分子來抑制腫瘤的生長和擴散。

Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4.

1. Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity. PMID: 30451856
2. Ndfip1 preserves Treg lineage stability and immune homeostasis by preventing the expansion of highly proliferative and metabolically active Treg cells and by preventing pathological secretion of IL-4 from Treg cells PMID: 28580955
3. IL-4/ STAT6 signaling needs to be well adjusted to ensure proper development and function of homing Th2 cells. PMID: 29738764
4. By establishing that IL-4 is posttranslationally regulated by TRX-promoted reduction of a disulfide bond, our findings highlight a novel regulatory mechanism of the type 2 immune response that is specific to IL-4 over IL-13. PMID: 30104382
5. The VEGFR1-mediated signaling suppressed IL-4-induced Arg-1 expression. PMID: 29110610
6. The results obtained in the present study suggest that a signaling pathway mediated by FcRg or the FcRg-Syk axis is commonly required for innate basophil IL-4 responses under conditions mimicking encounters with allergen sources. PMID: 26703455
7. IL-4Delta2 did not compete with IL-4 for IL-4Ralpha binding and did not interfere with the downstream STAT-6 phosphorylation in T cells. PMID: 28917204
8. this study shows that IL4 and IL21 cooperate to induce the high Bcl6 protein level required for germinal center formation PMID: 28875978
9. The complex role of IL-4 in autoimmunity and cholangitis. PMID: 27721424
10. The results demonstrate that IL-4 can restore insulin sensitivity in adipocytes via mechanisms not associated with induced adipogenesis or de novo formation of lipid depots. PMID: 29738684
11. Interleukin 4 (IL-4) signaling prevents Chlamydia trachomatis Infection from Inducing upper genital tract (UGT) pathology. PMID: 28765368
12. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)-dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection. PMID: 28495878
13. Data, including data from studies using transgenic mice, suggest that over-expression of IL4 (interleukin 4) in thyroid tissue/cells up-regulates expression of Duox1 (dual oxidase 1), Duoxa1 (dual oxidase maturation factor 1), and Slc26a4 (pendrin) in thyroid tissue/cells; expression of Slc5a5 (sodium-iodide symporter) is down-regulated. PMID: 27599561
14. we defined a molecular mechanism for IL-4 downregulation of involucrin in keratinocytes, which may play an important role in the pathogenesis of AD. PMID: 26918372
15. In this study, the effect of continuous IL-4 delivery or bioactive implant coating that constitutively releases a protein inhibitor of CCL2 signaling (7ND) on particle induced osteolysis were studied in the murine continuous femoral intramedullary particle infusion model PMID: 27114284
16. T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the lymph nodes. PMID: 27920023
17. Findings suggest that interleukin 4 (IL-4) affects anti-tumor immunity and constitutes an attractive therapeutic target to reduce immune suppression in the tumor microenvironment. PMID: 28733709
18. this study shows that environmental IL-4 plays a role in conditioning early thymic progenitors lineage choice, which would impact T cell development PMID: 28893952
19. this study shows that eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2(-/-) mice PMID: 27049063
20. findings show that during intestinal helminth infection, IL-4 derived from T follicular helper cells is required for IgE class switching and plasmablast formation PMID: 28533444
21. Data suggest that Il4 (usually released from helper T-cells) induces Cox1 in macrophages at post-transcriptional level; activation of Ampk (catalytic subunit Prkaa1) by metformin blocks Il4-dependent induction of Cox1 and blocks macrophage polarization/activation. (Il4 = interleukin-4; Cox1 = cyclooxygenase 1; Ampk = AMP-activated protein kinase) PMID: 28684424
22. IL-4 is required for the development of ex-Foxp3 T helper 2 cells. PMID: 28507062
23. conclude that a state of haploinsufficiency for the Il4 gene locus is specifically relevant for IL-4-dependent IgE responses to allergens with the amount of IL-4 produced in the hemizygous condition falling close to the threshold required for switching to IgE production PMID: 28115531
24. priming of T helper cells by IL-6-deficient antigen-presenting dendritic cells preferentially leads to accumulation of a subset of Follicular helper T cells characterized by high expression of GATA3 and IL-4. PMID: 27474166
25. eosinophils drive progression of myocarditis to Inflammatory dilated cardiomyopathy (DCMi), cause severe DCMi when present in large numbers, and mediate this process through IL-4. PMID: 28302646
26. These data suggest that although IL-4-stimulated alternatively activated macrophages upregulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative, rather than causative, role in systemic metabolic dysfunction. PMID: 28223293
27. Excessive IL-4 levels in the mesenteric lymph nodes (MLNs) directly inhibited the induction of aiTregs and caused enteropathy. The aiTregs generated in the attenuation of T cell-dependent food allergic enteropathy may function differently than aiTregs induced in a tolerance model. PMID: 28234975
28. this study shows that wild-type mice develop an eosinophilic Th2 airway disease in response to Alternaria alternata exposure, whereas IL-4-deficient mice exhibit a primarily neutrophilic response PMID: 27815425
29. Study showed that the intraperitoneal administration of the exogenous cytokines IFN-gamma (to promote M1 microglia ) and IL-4 (to promote M2 microglia) can correctly modulate the timing of the M1 to M2 ratio to affect epileptogenesis and to improve cognitive function in pilocarpine-induced status epilepticus. PMID: 27956120
30. These findings indicate that IL-4, a canonical Th2 cell cytokine, can sometimes promote rather than impair Th1 cell-type immune responses PMID: 27298446
31. Keratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease PMID: 27554818
32. Data show that lactic acid in tumor microenvironments inhibited interferon-gamma (IFNgamma) and intert=leukin-4 (IL4) productions from NKT cells by inhibiting mammalian target of rapamycin (mTOR) signaling. PMID: 27995420
33. this study shows that IL-4-mediated control of the precursor population affects the development of virus-specific CD8+ T-cell memory PMID: 27457412
34. IL-4 secretion by group 2 innate lymphoid cells contributes to the allergic response in food allergy by reducing allergen-specific Treg cell and activating mast cell counts PMID: 27177780
35. These studies clearly show a crucial role for IL-4 in the induction of airway hyperresponsiveness following Strongyloides venezuelensis infection and for IL-33/ST2 in maintaining airway hyperresponsiveness and lung Th2 responses. PMID: 27102638
36. we used recombinant herpes simplex virus vector S4IL4 that encode mouse il4 gene to evaluate the therapeutic potential of IL-4 in naloxone-precipitation morphine withdrawal (MW). One week after microinjection of the vector S4IL4 into the PAG LacZ or mouse IL-4 immunoreactivity in the vlPAG was visualized. ELISA assay showed that vector S4IL4 into the PAG induced the expression of IL-4 PMID: 28206989
37. this study shows that IL-4 is increased in the brain of T cell receptor transgenic mice, which exhibit impaired memory and adult hippocampal neurogenesis PMID: 27432189
38. this study shows that il-4 plays an important role in ESAT-6-induced MCP-1 production by macrophages, and suggest a pathway with significance in tuberculosis pathogenesis PMID: 27154637
39. indicate that Siglec-9 affects several different signaling pathways in IL-4-stimulated macrophages, which resulted in enhanced induction of Arg1 in Siglec-9-expressing RAW264 cells PMID: 26540411
40. Oct-1 and Oct-2 bound within the Il4 promoter region and the Th2 LCR PMID: 26840450
41. Loss of IL-4 promoted expression of M1 microglia/macrophage markers and impaired expression of M2 markers after transient or permanent middle cerebral artery occlusion. PMID: 26732561
42. These results indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing T-follicular helper cells. PMID: 26278622
43. IL-4 induces miR-142-5p and downregulates miR-130a-3p in macrophages, regulating macrophage profibrogenic gene expression in chronic inflammation. PMID: 26436920
44. these findings underscore the important collaboration between IL-4 and IL-21 in shaping T-dependent B cells antibody responses. PMID: 26491200
45. IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety PMID: 25772794
46. physiologic doses of interleukin-4 (IL-4) and interleukin-13 (IL-13) have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration PMID: 26039103
47. Concerted activity of IgG1 antibodies and IL-4/IL-25-dependent effector cells trap helminth larvae in the tissues following vaccination with defined secreted antigens, providing sterile immunity to challenge infection. PMID: 25816012
48. may be an important factor in providing 1,25D3-induced protection from experimental autoimmune encephalomyelitis PMID: 25574039
49. IL-4-producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response. PMID: 26363056
50. RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4. PMID: 26416964

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Secreted.

IL-4/IL-13 family

KEGG: mmu:16189

STRING: 10090.ENSMUSP00000000889

UniGene: Mm.276360