# The role of miRNAs in the development of Super-Tregs as a potential therapy for neurodegenerative diseases **Authors:** Kamalika Mukherjee, Suvendra N. Bhattacharyya PMC · DOI: 10.3389/fimmu.2026.1708031 · Frontiers in Immunology · 2026-02-04 ## TL;DR This paper reviews how miRNA-engineered Super-Tregs could be used to reduce neuroinflammation and treat diseases like Alzheimer's and Parkinson's. ## Contribution The paper highlights the novel use of miRNAs and extracellular vesicles to engineer enhanced anti-inflammatory Tregs for neurodegenerative disease therapy. ## Key findings - Impaired Treg function contributes to autoimmunity and neuroinflammation. - Super-Tregs can be engineered in vitro to suppress inflammation in neurodegenerative diseases. - miRNA-based modifications offer a promising approach to enhance Treg function for therapeutic use. ## Abstract Regulatory T cells, or Tregs, are designed to limit unnecessary inflammation and serve as a safeguard mechanism to prevent tissue damage caused by heightened inflammatory responses from activated macrophages or effector T cells. Impaired Treg function has implications in autoimmunity and neuroinflammation. Neuroinflammation triggered by amyloid proteins and protein aggregates accelerates neurodegeneration due to increased cytokines and chemokines in the brains of individuals with Alzheimer’s Disease and Parkinson’s Disease. A simple approach involves preventing inflammation by suppressing T-effector cell activity in affected brains through boosting Tregs’ function. Super-Tregs, with enhanced anti-inflammatory properties, can be engineered in vitro to combat inflammation in various tissues and, after homotropic transfer to the target tissue, prevent damage caused by inflammation. The development of Super-Tregs can be achieved through specific genetic and epigenetic modifications. Efforts to generate Super-Tregs utilizing miRNAs and miRNA-containing extracellular vesicles hold promise in treating neuroinflammation with miRNA-engineered Super-Tregs. In this review, we discuss the potential, progress, challenges, and limitations of Super-Treg development and their application in the treatment of neurodegeneration. ## Linked entities - **Diseases:** Alzheimer’s Disease (MONDO:0004975), Parkinson’s Disease (MONDO:0005180) ## Full-text entities - **Genes:** Icam1 (intercellular adhesion molecule 1) [NCBI Gene 15894] {aka CD54, Icam-1, Ly-47, MALA-2}, Pten (phosphatase and tensin homolog) [NCBI Gene 19211] {aka 2310035O07Rik, A130070J02Rik, B430203M17Rik, MMAC1, PTENbeta, TEP1}, Ccr6 (C-C motif chemokine receptor 6) [NCBI Gene 12458] {aka CC-CKR-6, CCR-6, Cmkbr6, KY411}, Cxcr3 (C-X-C motif chemokine receptor 3) [NCBI Gene 12766] {aka Cd183, Cmkar3}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 20846] {aka 2010005J02Rik}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Itgal (integrin alpha L) [NCBI Gene 16408] {aka (p180), Cd11a, LFA-1, LFA-1A, Ly-15, Ly-21}, Prdm1 (PR domain containing 1, with ZNF domain) [NCBI Gene 12142] {aka Blimp-1, Blimp1, PRDI-BF1, ZNFPR1A1, b2b1765Clo}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mir17hg (Mir17 host gene (non-protein coding)) [NCBI Gene 75957] {aka 5033413D16Rik, Mirhg1, mir-17-92}, Il11 (interleukin 11) [NCBI Gene 16156] {aka IL-11}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, Irak1 (interleukin-1 receptor-associated kinase 1) [NCBI Gene 16179] {aka IRAK, IRAK-1, IRAK1-S, IRAK1b, Il1rak, Plpk}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Mir146 (microRNA 146) [NCBI Gene 387164] {aka Mirn146, miR-146a, mmu-mir-146}, MIR145 (microRNA 145) [NCBI Gene 406937] {aka MIRN145, miR-145, miRNA145}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, Cx3cr1 (C-X3-C motif chemokine receptor 1) [NCBI Gene 13051] {aka mCX3CR1}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, IKZF2 (IKAROS family zinc finger 2) [NCBI Gene 22807] {aka ANF1A2, HELIOS, ICHAD, IMDIA, ZNF1A2, ZNFN1A2}, Lag3 (lymphocyte-activation gene 3) [NCBI Gene 16768] {aka CD223, LAG-3, Ly66}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Stat5a (signal transducer and activator of transcription 5A) [NCBI Gene 20850] {aka STAT5}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Mir27a (microRNA 27a) [NCBI Gene 387220] {aka Mirn27a, mir-27a, mmu-mir-27a}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, TNFRSF25 (TNF receptor superfamily member 25) [NCBI Gene 8718] {aka APO-3, DDR3, DR3, LARD, TNFRSF12, TR3}, Thy1 (thymus cell antigen 1, theta) [NCBI Gene 21838] {aka CD90, T25, Thy-1, Thy-1.2, Thy1.1, Thy1.2}, Aire (autoimmune regulator) [NCBI Gene 11634], Mir17 (microRNA 17) [NCBI Gene 723905] {aka Mirn17, mir-17, mmu-mir-17}, Il22 (interleukin 22) [NCBI Gene 50929] {aka IL-22, IL-22a, ILTIFa, If2b1, Iltif}, Qrsl1 (glutaminyl-tRNA synthase (glutamine-hydrolyzing)-like 1) [NCBI Gene 76563] {aka 2700038P16Rik, GatA}, Cd19 (CD19 antigen) [NCBI Gene 12478], Smarca4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) [NCBI Gene 20586] {aka BAF190A, Brg1, HP1-BP72, SNF2beta, SW1/SNF, b2b508.1Clo}, Cxcl14 (C-X-C motif chemokine ligand 14) [NCBI Gene 57266] {aka 1110031L23Rik, 1200006I23Rik, BMAC, BRAK, KS1, Kec}, Mir142 (microRNA 142) [NCBI Gene 387160] {aka Mirn142, miR-142, mir-142a, mmu-mir-142, mmu-mir-142a}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mir137 (microRNA 137) [NCBI Gene 387155] {aka Mirn137, mir-137, mmu-mir-137}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17} - **Diseases:** asthma (MESH:D001249), DLB (MESH:D020961), anxiety (MESH:D001007), Neuroinflammation (MESH:D000090862), brain atrophy (MESH:C566985), neuropsychiatric conditions (MESH:D001523), AD (MESH:D000544), inflammatory neurotoxicity (MESH:D020258), cancer (MESH:D009369), lupus nephritis (MESH:D008181), sleep, (MESH:D012893), Alzheimer's and Parkinson's (MESH:D010300), degenerative and autoimmune disorders (MESH:D019636), injury (MESH:D014947), Inflammatory (MESH:D007249), loss (MESH:D016388), SLE (MESH:D008180), neuroblastoma (MESH:D009447), fatigue difficulties (MESH:D005221), stroke (MESH:D020521), allergic conjunctivitis (MESH:D003233), autoimmune (MESH:D001327), microbial infections (MESH:D015163), tauopathies (MESH:D024801), toxicity (MESH:D064420), infected (MESH:D007239), Brain (MESH:D001927), bradykinesia (MESH:D018476), tremor (MESH:D014202), astrogliosis (MESH:D005911), ALS (MESH:D000690), glioblastoma (MESH:D005909), dopaminergic neuronal damage (MESH:D009422), cognitive deficits (MESH:D003072), brain tumor (MESH:D001932), infectious (MESH:D003141), multiple sclerosis (MESH:D009103), rigidity (MESH:D009127), EOS (MESH:C538157), balance, coordination, and muscle control deficits (MESH:D009135), Lewy (MESH:D018827), amyloid (MESH:C000718787), dementia (MESH:D003704), Type 1 diabetes (MESH:D003922), dopaminergic neuron degeneration (MESH:D009410), inflammatory bowel disease (MESH:D015212), depression (MESH:D003866) - **Chemicals:** rapamycin (MESH:D020123), adenosine (MESH:D000241), 5-methylcytosine (MESH:D044503), amino acids (MESH:D000596), 5-hydroxymethylcytosine (MESH:C011865), FOXP3CAR (-), glucose (MESH:D005947), calcium (MESH:D002118), dopamine (MESH:D004298), Lipid (MESH:D008055) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Collinsella (genus) [taxon 102106], Legionella sp. D (species) [taxon 66972], gut metagenome (species) [taxon 749906], Leishmania donovani (species) [taxon 5661] - **Mutations:** L286V, A53T, M146L, rs429358 ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12914384/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12914384/full.md ## References 252 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914384/full.md --- Source: https://tomesphere.com/paper/PMC12914384