T细胞活化原理与诱导分化全攻略

T淋巴细胞作为免疫系统的重要成员，是适应性免疫系统的核心执行者，更是机体抗肿瘤免疫应答的终极效应细胞。基础研究中，研究者常分离扩增初始T细胞，通过特定细胞因子组合定向诱导其分化为Th1/Th2/Th17/Treg等亚群，进而解析各亚群的生物学功能与效应机制。T细胞的活化是上述分化与功能研究的前提——无论是模拟生理性T细胞受体信号及CD28共刺激（辅以IL-2维持扩增），还是采用佛波酯与离子霉素进行短时强效刺激以检测效应表型，均需建立在对活化原理的清晰理解之上。因此，掌握T细胞活化诱导的原理与标准化鉴定方法，是深入理解免疫调控机制、获得可重复实验结果的基石。

一、T细胞活化原理

T细胞起源于骨髓造血干细胞，在胸腺中发育成熟，此过程中通过阳性选择和阴性选择获得MHC限制性。成熟的T细胞进入血液循环，随后分布于外周淋巴器官（如淋巴结、脾脏），等待抗原刺激。T细胞的完全活化需要三个信号协同作用，缺一不可，共同确保免疫应答的特异性和可控性。

信号一：TCR特异性识别抗原呈递细胞（APC）呈递的MHC-抗原复合物

MHC-I：呈递内源性抗原给CD8⁺ T细胞（细胞毒性T细胞）。

MHC-II：呈递外源性抗原给CD4⁺ T细胞（辅助性T细胞）。

信号二：共刺激信号，非特异性，确保T细胞在正确环境中被激活，实现完全活化

正共刺激信号：如CD28识别CD80/CD86；

负共刺激信号：如CTLA-4-CD80/CD86抑制活化的或效应T细胞过度活化；

信号三：由APC分泌的炎症性细胞因子及免疫微环境中的其他细胞因子共同组成，促进T细胞增殖、效应功能发育及分化方向决定

如IL-12、I型干扰素以及T细胞自分泌的IL-2等。

T细胞接受了三个信号后，退出G0期，进入激活状态。激活后的T细胞表现出高度的增殖能力，并分泌大量细胞因子以进一步激活其他免疫细胞。

初始CD4⁺T细胞的激活条件doi.org/10.1016/j.it.2023.04.004

二、体外活化T细胞的常用刺激物

1. CD3/CD28抗体：如CD3/CD28抗体、以及抗体偶联的磁珠或包被抗体的培养板；常联合IL-2促进T细胞活化增殖；

2. 佛波酯（PMA）：该化合物是蛋白激酶C（PKC）的强效激活剂，可模拟二酰甘油（DAG）功能，直接结合并激活PKC，从而绕过T细胞受体（TCR）复合物激活下游信号通路；

3. 离子霉素（ionomycin）：属于钙离子载体，使钙离子内流，提高细胞内的钙离子水平，激活钙调蛋白酶和丝裂原活化蛋白磷酸酶；离子霉素通常与PMA联合使用，因为PMA激活PKC，两者协同完全激活T细胞（NF-κB和NFAT通路）；

4. 抗原非依赖性丝裂原：植物血凝素（PHA）和刀豆凝集素（ConA），通过使T细胞表面糖蛋白受体发生交联引发相关的信号级联反应，进而使T细胞活化增殖；

5. 细胞因子：IL-2可以与其他刺激物联用促进T细胞活化增殖，IL-7和IL-15也可以促进T细胞活化增殖；

三、人Th亚群诱导分化方案

准备培养基：1640培养基，血清(胎牛)，双抗，L-谷氨酰胺，β-巯基乙醇

培养基配置：RPMI-1640+10%胎牛血清+1mM L-谷氨酰胺+55μM β-巯基乙醇+双抗

准备细胞：分选出Naive CD4⁺T cells(CD4⁺CD25^-CD44^lowCD62L^high)

细胞刺激培养：

1. CD3包板：包板浓度2 μg/mL (96孔板加50μL，48孔板加200μL )，加入上述体积后4度过夜包被，包被后弃去孔内液体，PBS洗板1次；

2. 分选的Naive CD4⁺ T cells加入包被孔内；

a) 96孔板加入1*10⁵细胞（200μL培养体系）

b) 48孔板加入2*10⁵细胞（500μL培养体系）

3. 配置分化培养基(4 μg/mL anti-human CD28 +10 ng/mL Human IL-2)

根据需要分化的方向额外添加以下成分:

a) TH1，IL-12(50 ng/mL) plus anti-human IL-4(10 μg/mL)

b) TH2，IL-4(50 ng/mL) plus anti-human IFN-γ(10 μg/mL)

c) TH17，IL-6(50 ng/mL), IL-1B(10 ng/mL), IL-23(10 ng/mL), TGF-β(10 ng/mL) plus anti-human IFN-γ(10 μg/mL) and IL-4(10 μg/mL)

d) iTreg，TGF-β (10 ng/mL) plus anti-human IFN-γ (10 μg/mL) and IL-4 (10 μg/mL)

e) TH9，IL-4 (50 ng/mL), TGF-β (10 ng/mL), plus anti-human IFN-γ(10 μg/mL)

f) TH22，IL-6 (50 ng/mL), IL-23 (50 ng/mL), plus anti-human IFN-γ (10 μg/mL) and IL-4 (10 μg/mL)

g) Tfh，IL-6 (50 ng/mL), IL-21 (10 ng/mL), CXCL13 (10 ng/mL):

4. 细胞培养分化3-5天，培养过程中若培养液上清变黄，更换培养基，一般建议半量换液，根据培养经验，一般是隔天换液。

5. 培养分化后鉴定(胞内染色)：分化后的细胞加入20 ng/mL PMA，1 μg/mL Ionomycin刺激30 min后，加入10 μg/mL BFA阻断，继续培养3.5h后收集细胞进行流式检测。(见Th亚群鉴定章节)

6. 细胞鉴定：购买相应的流式抗体及辅助试剂进行胞内染色鉴定，常见的鉴定指标如下图所示。

Tips：高质量的重组细胞因子是实验成功的关键。我们推荐使用无载体蛋白（Carrier-Free） 的重组细胞因子（如PeproTech相关产品），以避免载体蛋白对细胞培养可能产生的干扰。

四、细胞分化所需细胞因子与抗体

五、细胞鉴定所需试剂

六、产品相关参考文献

BioGems产品CD3与CD28激活抗体

[1] Li C, Lin Y, Zheng H, et al. Glutamate transporter SLC1A6 promotes resistance to immunotherapy in cancer. Cancer Immunol Immunother. 2025;74(8):240. Published 2025 Jun 7. doi:10.1007/s00262-025-04074-4

[2] Xu G, Wang J, Qu Y, et al. GSTP1 improves CAR-T cell proliferation and cytotoxicity to combat lymphoma. Front Immunol. 2025;16:1665407. Published 2025 Sep 26. doi:10.3389/fimmu.2025.1665407

[3] Chen X, Huang D, Zhao L, et al. Fluvastatin Promotes Treg Cell Production in Allogeneic Immune Reaction and Suppresses Inflammatory Response. Immun Inflamm Dis. 2025;13(2):e70165. doi:10.1002/iid3.70165

[4] Fan Z, Yi Z, Li S, He J. Parabacteroides distasonis promotes CXCL9 secretion of tumor-associated macrophages and enhances CD8+T cell activity to trigger anti-tumor immunity against anti-PD-1 treatment in non-small cell lung cancer mice. BMC Biotechnol. 2025;25(1):30. Published 2025 Apr 16. doi:10.1186/s12896-025-00963-9

[5] Mai Q, Du Q, Zeng F, et al. Galectin-3 suppresses CD8+ T cells function via myeloid-derived suppressor cells recruitment in cervical cancer. Int J Biol Macromol. 2025;311(Pt 4):143683. doi:10.1016/j.ijbiomac.2025.143683

[6] Wang Y, Xiang Q, Wu Y, et al. Mesenchymal Stem Cell-Derived Exosomes Inhibit Stim1-Orai1 Signaling and Calcium Overload-Induced Mitochondrial Damage of Follicular Helper T Cells in Lupus. Biomater Res. 2025;29:0255. Published 2025 Sep 22. doi:10.34133/bmr.0255

[7] Wan D, Zhang Q, Yang Z, et al. Engineered oncolytic virus OH2-FLT3L enhances antitumor immunity via dendritic cell activation. Mol Ther Oncol. 2025;33(2):200975. Published 2025 Mar 21. doi:10.1016/j.omton.2025.200975

[8] Zhang Z, Yang Y, Chen Y, Su J, Du W. Malic enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells. Mol Cell. 2024;84(17):3354-3370.e7. doi:10.1016/j.molcel.2024.07.021

[9] Xu W, Hu M, Lu X, et al. Inhibition of PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy. Int J Biol Sci. 2024;20(10):3942-3955. Published 2024 Jul 15. doi:10.7150/ijbs.93668

[10] Zhang X, Chen R, Huo Z, et al. Blood-based molecular and cellular biomarkers of early response to neoadjuvant PD-1 blockade in patients with non-small cell lung cancer. Cancer Cell Int. 2024;24(1):225. Published 2024 Jun 29. doi:10.1186/s12935-024-03412-3

[11] Wang R, Li C, Cheng Z, et al. H3K9 lactylation in malignant cells facilitates CD8+ T cell dysfunction and poor immunotherapy response. Cell Rep. 2024;43(9):114686. doi:10.1016/j.celrep.2024.114686

[12] Tang D, Zhao L, Yan F, Ren C, Xu K, Zhao K. Expression of VISTA regulated via IFN-γ governs endogenous T-cell function and exhibits correlation with the efficacy of CD19 CAR-T cell treated B-malignant mice. J Immunother Cancer. 2024;12(6):e008364. Published 2024 Jun 25. doi:10.1136/jitc-2023-008364

[13] Dabbah-Krancher G, Ruchinskas A, Kallarakal MA, et al. A20 intrinsically influences human effector T-cell survival and function by regulating both NF-κB and JNK signaling. Eur J Immunol. 2024;54(12):e2451245. doi:10.1002/eji.202451245

[14] Yu W, Wang K, He Y, et al. The potential role of lung microbiota and lauroylcarnitine in T-cell activation associated with checkpoint inhibitor pneumonitis. EBioMedicine. 2024;106:105267. doi:10.1016/j.ebiom.2024.105267

[15] Zhang XY, Shi JB, Jin SF, et al. Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape. Cancer Commun (Lond). 2024;44(6):670-694. doi:10.1002/cac2.12545

[16] Wang X, Fang Y, Liang W, et al. Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer. Cancer Cell. 2024;42(10):1729-1746.e8. doi:10.1016/j.ccell.2024.08.019

[17] Wang F, Li Y, Yang Z, et al. Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. Nat Commun. 2024;15(1):203. Published 2024 Jan 3. doi:10.1038/s41467-023-44270-3

[18] Qian Y, Sun Y, Shi P, et al. Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy. Acta Pharm Sin B. 2024;14(3):1150-1165. doi:10.1016/j.apsb.2023.12.011

[19] Deng C, Xu Y, Chen H, et al. Extracellular-vesicle-packaged S100A11 from osteosarcoma cells mediates lung premetastatic niche formation by recruiting gMDSCs. Cell Rep. 2024;43(2):113751. doi:10.1016/j.celrep.2024.113751

[20] Jin S, Wang H, Li Y, et al. Discovery of a novel small molecule as CD47/SIRPα and PD-1/PD-L1 dual inhibitor for cancer immunotherapy. Cell Commun Signal. 2024;22(1):173. Published 2024 Mar 11. doi:10.1186/s12964-024-01555-4

[21] Feng S, Wang D, Jin Y, et al. Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity. Cell Rep. 2024;43(6):114300. doi:10.1016/j.celrep.2024.114300

[22] Ren H, Chen Y, Zhu Z, et al. FOXO1 regulates Th17 cell-mediated hepatocellular carcinoma recurrence after hepatic ischemia-reperfusion injury. Cell Death Dis. 2023;14(6):367. Published 2023 Jun 17. doi:10.1038/s41419-023-05879-w

[23] Fan W, Wang X, Zeng S, et al. Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis. Sci Adv. 2023;9(42):eadh4655. doi:10.1126/sciadv.adh4655

[24] Li P, Zhou D, Chen D, et al. Tumor-secreted IFI35 promotes proliferation and cytotoxic activity of CD8+ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer. J Biomed Sci. 2023;30(1):47. Published 2023 Jun 28. doi:10.1186/s12929-023-00930-6

[25] Shang S, Yang C, Chen F, et al. ID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer. Nat Commun. 2023;14(1):7661. Published 2023 Nov 23. doi:10.1038/s41467-023-43548-w

[26] Lkhagva-Yondon E, Seo MS, Oh Y, et al. The aryl hydrocarbon receptor controls mesenchymal stromal cell-mediated immunomodulation via ubiquitination of eukaryotic elongation factor-2 kinase. Cell Death Dis. 2023;14(12):812. Published 2023 Dec 9. doi:10.1038/s41419-023-06341-7

[27] Han K, Li SS, Pan W, et al. ERK/MEK Pathway Regulates Th17 Cell Differentiation in Patients with Pemphigus Vulgaris. Indian J Dermatol. 2023;68(6):724. doi:10.4103/ijd.ijd_924_22

[28] Han SM, Park ES, Park J, et al. Unique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice. Nat Commun. 2023;14(1):8512. Published 2023 Dec 21. doi:10.1038/s41467-023-44181-3

[29] Yu A, Hu J, Fu L, et al. Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8+ T cell infiltration and functional transition. J Immunother Cancer. 2023;11(10):e007230. doi:10.1136/jitc-2023-007230

[30] Cao W, Cao J, Li X, et al. A novel inducible haematopoietic cell-depleting mouse model for chimeric complementation of blood cells. Cell Prolif. 2023;56(5):e13472. doi:10.1111/cpr.13472

[31] Wang F, Qi Q, Qin B, et al. Targeting VCP potentiates immune checkpoint therapy for colorectal cancer. Cell Rep. 2023;42(11):113318. doi:10.1016/j.celrep.2023.113318

[32] Liu A, Liu Q, Leng S, et al. Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID. Clin Exp Immunol. 2023;211(1):68-77. doi:10.1093/cei/uxac121

[33] Nahmad AD, Reuveni E, Goldschmidt E, et al. Frequent aneuploidy in primary human T cells after CRISPR-Cas9 cleavage. Nat Biotechnol. 2022;40(12):1807-1813. doi:10.1038/s41587-022-01377-0

[34] Zhan Y, Cao J, Ji L, et al. Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing. Exp Hematol Oncol. 2022;11(1):48. Published 2022 Sep 1. doi:10.1186/s40164-022-00304-y

[35] Zhang Z, Ji W, Huang J, et al. Characterization of the tumour microenvironment phenotypes in malignant tissues and pleural effusion from advanced osteoblastic osteosarcoma patients. Clin Transl Med. 2022;12(11):e1072. doi:10.1002/ctm2.1072

[36] Huang H, Guo F, Deng X, et al. Modulation of T Cell Responses by Fucoidan to Inhibit Osteogenesis. Front Immunol. 2022;13:911390. Published 2022 Jun 23. doi:10.3389/fimmu.2022.911390

[37] Lee MH, Lee YS, Kim HJ, Han CH, Kang SU, Kim CH. Non-thermal plasma inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice. Sci Rep. 2019;9(1):13510. Published 2019 Sep 18. doi:10.1038/s41598-019-49938-9

[38] Kaisar-Iluz N, Arpinati L, Shaul ME, et al. The Bilateral Interplay between Cancer Immunotherapies and Neutrophils' Phenotypes and Sub-Populations. Cells. 2022;11(5):783. Published 2022 Feb 23. doi:10.3390/cells11050783

[39] Kim M, Kim SD, Kim KI, et al. Dynamics of T Lymphocyte between the Periphery and the Brain from the Acute to the Chronic Phase Following Ischemic Stroke in Mice. Exp Neurobiol. 2021;30(2):155-169. doi:10.5607/en20062

[40] Tan J, Liu H, Huang M, et al. Small molecules targeting RORγt inhibit autoimmune disease by suppressing Th17 cell differentiation. Cell Death Dis. 2020;11(8):697. Published 2020 Aug 22. doi:10.1038/s41419-020-02891-2

[41] Chen Z, Hu Y, Gong Y, et al. Interleukin-33 alleviates psoriatic inflammation by suppressing the T helper type 17 immune response. Immunology. 2020;160(4):382-392. doi:10.1111/imm.13203

[42] Xie Y, Zhang Y, Wei X, et al. Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells. Front Pharmacol. 2020;11:16. Published 2020 Feb 18. doi:10.3389/fphar.2020.00016

[43] Han J, Gao F, Geng S, et al. Minicircle DNA-Engineered CAR T Cells Suppressed Tumor Growth in Mice. Mol Cancer Ther. 2020;19(1):178-186. doi:10.1158/1535-7163.MCT-19-0204

[44] Li S, Feng J, Wu F, et al. TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8+ T-cell numbers. EMBO Rep. 2020;21(10):e49425. doi:10.15252/embr.201949425

[45] Jang SE, Jeong JJ, Choi SY, Kim H, Han MJ, Kim DH. Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14 Attenuate Gardnerella vaginalis-Infected Bacterial Vaginosis in Mice. Nutrients. 2017;9(6):531. Published 2017 May 23. doi:10.3390/nu9060531

BioGems产品Transcription Factor Fixation/Permeabilization固定破膜剂

[1] Zhou T, Wu Y, Li S, et al. Multi-omic analysis of gallbladder cancer identifies distinct tumor microenvironments associated with disease progression. Nat Genet. 2025;57(8):1935-1949. doi:10.1038/s41588-025-02236-9

[2] Liu C, Ma R, Li H, et al. Akkermansia muciniphila ameliorates fatty liver through microbiota-derived α-ketoisovaleric acid metabolism and hepatic PI3K/Akt signaling. iScience. 2025;28(5):112458. Published 2025 Apr 16. doi:10.1016/j.isci.2025.112458

[3] Zhang Z, Yang Y, Chen Y, Su J, Du W. Malic enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells. Mol Cell. 2024;84(17):3354-3370.e7. doi:10.1016/j.molcel.2024.07.021

[4] Acúrcio RC, Kleiner R, Vaskovich-Koubi D, et al. Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy. Adv Sci (Weinh). 2024;11(40):e2404159. doi:10.1002/advs.202404159

[5] Zhang XY, Shi JB, Jin SF, et al. Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape. Cancer Commun (Lond). 2024;44(6):670-694. doi:10.1002/cac2.12545

[6] Luo Y, Liu F, Deng L, et al. Innate and Adaptive Immune Responses Induced by Aspergillus fumigatus Conidia and Hyphae. Curr Microbiol. 2022;80(1):28. Published 2022 Dec 6. doi:10.1007/s00284-022-03102-1

[7] Watson A, Li H, Ma B, et al. Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis. Nat Commun. 2021;12(1):602. Published 2021 Jan 27. doi:10.1038/s41467-021-20930-0

[8] Zhang S, Ji WW, Wei W, Zhan LX, Huang X. Long noncoding RNA Meg3 sponges miR-708 to inhibit intestinal tumorigenesis via SOCS3-repressed cancer stem cells growth. Cell Death Dis. 2021;13(1):25. Published 2021 Dec 21. doi:10.1038/s41419-021-04470-5

[9] Zhang Z, Wang H, Xie X, et al. Long-Residence Pneumonia Vaccine Developed Using PEG-Grafted Hybrid Nanovesicles from Cell Membrane Fusion of Mycoplasma and IFN-γ-Primed Macrophages. Small. 2021;17(34):e2101183. doi:10.1002/smll.202101183

[10] Zhang Z, Wang H, Xie X, et al. Long-Residence Pneumonia Vaccine Developed Using PEG-Grafted Hybrid Nanovesicles from Cell Membrane Fusion of Mycoplasma and IFN-γ-Primed Macrophages. Small. 2021;17(34):e2101183. doi:10.1002/smll.202101183

[11] Li Z, Zheng B, Qiu X, et al. The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma. NPJ Precis Oncol. 2020;4:28. Published 2020 Oct 30. doi:10.1038/s41698-020-00133-4

[12] Zheng B, Wang D, Qiu X, et al. Trajectory and Functional Analysis of PD-1high CD4+CD8+ T Cells in Hepatocellular Carcinoma by Single-Cell Cytometry and Transcriptome Sequencing. Adv Sci (Weinh). 2020;7(13):2000224. Published 2020 May 18. doi:10.1002/advs.202000224

[13] Zhou WJ, Zhang J, Yang HL, et al. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism. Cell Commun Signal. 2019;17(1):99. Published 2019 Aug 20. doi:10.1186/s12964-019-0412-9

BioGems产品PMA-Ionomycin-BFA

[1] Liu Q, Liu A, Leng S, et al. Itaconate derivative 4-OI inhibits M1 macrophage polarization and restores its impaired function in immune thrombocytopenia through metabolic reprogramming. Chin Med J (Engl). 2025;138(16):2006-2015. doi:10.1097/CM9.0000000000003586

[2] Ma J, Tang L, Tan Y, et al. Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria. Nat Immunol. 2024;25(3):552-561. doi:10.1038/s41590-023-01738-0

[3] Liu Z, Duan X, Yun Y, et al. Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice. ACS Nano. 2024;18(4):3826-3838. doi:10.1021/acsnano.3c12499

[4] Liu A, Liu Q, Leng S, et al. Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID. Clin Exp Immunol. 2023;211(1):68-77. doi:10.1093/cei/uxac121

[5] Karagiannis F, Peukert K, Surace L, et al. Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19. Nature. 2022;609(7928):801-807. doi:10.1038/s41586-022-05128-8

[6] Li W, Chen JY, Sun C, et al. Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells. Elife. 2022;11:e74513. Published 2022 May 26. doi:10.7554/eLife.74513

[7] Chen Y, Huang H, Liu Y, et al. Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy. Cancer Res Treat. 2022;54(2):362-374. doi:10.4143/crt.2021.424

[8] Reustle A, Menig LS, Leuthold P, et al. Nicotinamide-N-methyltransferase is a promising metabolic drug target for primary and metastatic clear cell renal cell carcinoma. Clin Transl Med. 2022;12(6):e883. doi:10.1002/ctm2.883

[9] Zeng Y, Zhang Y, Huang X, et al. Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide. Respir Res. 2021;22(1):263. Published 2021 Oct 10. doi:10.1186/s12931-021-01850-5

[10] Tian J, Kou X, Wang R, et al. Autophagy controls mesenchymal stem cell therapy in psychological stress colitis mice. Autophagy. 2021;17(9):2586-2603. doi:10.1080/15548627.2020.1821547

[11] Cheng K, Du T, Li Y, et al. Dual-Antigen-Loaded Hepatitis B Virus Core Antigen Virus-like Particles Stimulate Efficient Immunotherapy Against Melanoma. ACS Appl Mater Interfaces. 2020;12(48):53682-53690. doi:10.1021/acsami.0c16012

[12] Zhang J, Chen C, Fu H, et al. MicroRNA-125a-Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Restoring Effector/Regulatory T Cells Balance. ACS Nano. 2020;14(4):4414-4429. doi:10.1021/acsnano.9b09998

[13] Zhang J, Sun Z, Wu Q, Shen J. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells. Immunol Lett. 2020;219:8-14. doi:10.1016/j.imlet.2019.12.008

[14] Liu Z, Gu J, Qin Z, et al. Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation. Ann Transl Med. 2020;8(8):534. doi:10.21037/atm.2020.03.203

[15] Li Y, Jia A, Wang Y, et al. Immune effects of glycolysis or oxidative phosphorylation metabolic pathway in protecting against bacterial infection. J Cell Physiol. 2019;234(11):20298-20309. doi:10.1002/jcp.28630