RARE DISEASE
Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome
Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome
Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome
Synonyms: Autoimmune enteropathy type 1, IPEX
Synonyms: Autoimmune enteropathy type 1, IPEX
Synonyms: Autoimmune enteropathy type 1, IPEX
Drug discovery
2
drugs
With orphan designations
Overview
Immune Dysregulation-Polyendocrinopathy-Enteropathy-X-Linked (IPEX) Syndrome: A rare X-linked recessive disorder caused by FOXP3 gene mutations, impairing regulatory T-cell function and causing severe multiorgan autoimmunity. Core features include autoimmune enteropathy (90-100% cases), type 1 diabetes (60-80%), and dermatitis (60-70%). Untreated mortality exceeds 90% by age 2 [1][6][13]. Diagnosis combines clinical triad, genetic testing, and low FOXP3+ Treg cells [1][4][6].
Therapies
Immediate: Immunosuppression (tacrolimus/sirolimus ± corticosteroids) for symptom control [6][13]
Curative: Allogeneic HSCT achieves 75-85% survival if performed pre-organ damage [7][10][13]
Emerging: Autologous Treg engineering [3][10] and FOXP3 gene editing in HSPCs [3][10] show preclinical efficacy
Categories: rare endocrine diseases, rare gastroenterological diseases, rare genetic diseases, rare immunological diseases, rare transplant-related disorders
Research Papers
516 drug discovery papers about Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, with 5 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
516 drug discovery papers about Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, with 5 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-28 | Limosilactobacillus reuteri-educated T cells protect against activation of liver inflammation in immunocompromised mice 2229185
Abstract Introduction Oral administration of probiotic Limosilactobacillus reuteri DSM 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in Treg-deficient scurfy (SF) mice, which model human IPEX syndrome. It is unclear how DSM 17938 educated SF-CD4+T cells can facilitate T cell-liver communication. Methods We adoptively transferred by intraperitoneal injection cells isolated from SF spleens into lymphocyte-deficient-RAG1KO mice and compared the CD4+T cells from SF mice gavage-fed with DSM 17938 with the CD4+T cells from untreated SF mice (Prob-SF-CD4+T cells versus SF-CD4+T cells). Liver inflammatory histology and transcriptomes in RAG1KO mice were analyzed. Results We observed that Prob-SF-CD4+T cells reduced the incidence and severity of liver inflammation caused by transferring SF-CD4+T cells. SF-CD4+T cells up-regulated expression of liver genes involved in TLR cascades, inflammatory cytokine and death receptor signals, while down-regulated genes linked to mitochondrial respiratory chain complexes, TCA cycle, liver detoxification and lipid metabolism. However, Prob-SF-CD4+T cell transfer reversed SF-CD4+T cell-induced transcriptomic changes in inflammatory and metabolic clusters by modulating distinct genes participating in TLR regulation, mitochondrial function and cell cycle. Conclusion In conclusion, inflammatory CD4+T cells can perpetuate an exaggerated immune response in the immunologically naïve host. DSM17938 has the capacity to reprogram inflammatory CD4+T cells and allowed them to benefit the recipient. Probiotic-modulated T cells can be further explored as a therapeutic option for autoimmune liver diseases. Funding Source National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) R03AI153725 Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-28 | Targeting the FOXP3—T-bet interaction to restore Treg stability in IFN-γ—driven autoimmunity 2254306
Abstract Introduction Regulatory T cells (Tregs) maintain immune homeostasis through FOXP3-centered transcriptional complexes that tightly control lineage stability and suppressive function. However, how specific FOXP3 mutations disturb this complex and drive pathogenic Treg reprogramming in IPEX syndrome remains unclear. We identified a distinctive mechanism by which the FOXP3 V408M mutation promotes Th1-skewed inflammation and also explored a pharmacological strategy to restore Treg stability. Methods We generated FOXP3 V408M knock-in mice and performed immunophenotyping, transcriptomic, and chromatin conformation analyses to determine how the mutation affects FOXP3—T-bet interaction and Ifng transcription. An AI-driven virtual screening strategy integrating sequence- and structure-based modeling was applied to identify compounds that stabilize FOXP3—T-bet interaction. Functional validation was performed in vitro and in multiple in vivo mouse models. Results FOXP3 V408M mutation disrupted the FOXP3—T-bet interaction, thereby releasing T-bet from FOXP3-mediated repression and enhancing Ifng transcription. This defect reprogrammed Tregs toward an IFN-γ—producing phenotype that promoted Th1 inflammation. Among the AI-driven screening hits, 430C10 emerged as a first-in-class FOXP3-targeting stabilizer binding an allosteric pocket within the FKH domain. 430C10 reinforced the FOXP3—T-bet interaction and suppressed T-bet—driven IFN-γ production by Tregs. Oral 430C10 treatment markedly alleviated IFN-γ+ Treg—driven inflammation in FOXP3 V408M mice and improved disease outcomes in an acute colitis model under FOXP3 WT settings. Conclusion Our findings define the FOXP3—T-bet interaction as a tunable checkpoint controlling Treg stability and IFN-γ—driven autoimmunity. Pharmacological stabilization of this interaction with 430C10 provides a proof-of-concept therapeutic strategy for restoring immune homeostasis in IPEX syndrome and related autoimmune diseases. Funding Source Our research is supported by National Natural Science Foundation of China (82271829, 32130041, 82441047, 82241222); The Innovation Program of Shanghai Municipal Education Commission (21140902900); Noncommunicable Chronic Diseases-National Science and Tech Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-06-26 | FOXP3 Mutations and Instability as Determinants of Regulatory T-Cell Plasticity in Endocrine Autoimmunity
Autoimmune endocrine diseases constitute a group of disorders characterized by immune-mediated destruction or dysfunction of hormone-producing glands. The pathogenesis of these diseases reflects a breakdown of immune tolerance in which regulatory T cells (Tregs) play a key role. The transcription factor forkhead box P3 (FOXP3) is a master regulator of Treg differentiation and suppressive function. Also, it is central to maintaining self-tolerance. Genetic mutations in FOXP3, including those responsible for immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, highlight the critical role of FOXP3 in endocrine immune tolerance. Emerging evidence suggests that autoimmune endocrine disorders may reflect organ-specific destabilization of FOXP3 expression rather than complete Treg deficiency. The reversibility or irreversible loss of FOXP3 gene expression represents a key determinant of Treg plasticity and the persistence of autoimmune inflammation. This review proposes an integrated genetic–epigenetic model of FOXP3 instability and examines how the endocrine microenvironment shapes Treg plasticity. Genetic or epigenetic alterations affecting FOXP3 expression can impair Treg activity and precipitate endocrine organ-specific autoimmunity. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA-mediated regulation that modulate FOXP3 transcriptional activity are discussed. From a translational perspective, the potential of FOXP3 as a biomarker for endocrine disease susceptibility and progression was summarized. Furthermore, therapeutic strategies employed for expanding or engineering functional FOXP3+ Tregs using antigen-specific vaccines, chimeric antigen receptors (CAR)-Tregs, gene therapy, or low-dose interleukin-2 (IL-2) were described.
2026-05-01 | Peripheral Expression of FOXP3 in Brazilian Patients with IPEX Syndrome: From FOXP3 Biomarker to Targeted FOXP3 Therapy Within the CNE3I
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder caused by loss-of-function mutations in the FOXP3 gene, which is critical for the development of functional regulatory T cells (Tregs). In IPEX patients, Tregs are unable to inhibit effector T cell proliferation and cytokine production, leading to a loss of peripheral immune tolerance. The disease presents with heterogeneous clinical manifestations, severe early-onset autoimmunity, the classic triad (enteropathy, eczema, and type 1 diabetes), as well as atypical or late-onset symptoms. A clear genotype–phenotype correlation has not been established for IPEX, and immunological assessments that could contribute to the diagnosis are scarce. Therefore, we aim to characterize the peripheral Treg cells in IPEX patients in Brazil through combined quantitative and qualitative flow cytometry analysis. We enrolled 6 male patients with a confirmed IPEX diagnosis (clinical, genetic, and immunological). All patients exhibited autoimmunity (enteropathy: 5/6; arthritis: 3/6; hemolytic anemia: 2/6; type 1 diabetes: 2/6), and allergic manifestations (rhinitis: 6/6; asthma: 4/6), eczema (4/6), and recurrent sinusitis (4/6) were also observed. Up to the last follow-up, two patients were alive after bone marrow transplantation and one after gene therapy (Figure 1). Peripheral FOXP3 expression was assessed in peripheral blood mononuclear cells (PBMCs) by flow cytometry (CD3, CD4, CD25, CD127, and FOXP3). Quantitative analysis determined the frequency of Tregs (CD4+CD25+CD127-FOXP3+), while qualitative analysis measured FOXP3 protein expression via median fluorescence intensity (MFI). The frequency of circulating Tregs in IPEX patients from our cohort was highly variable (14.6%–81.2%; mean: 58.5%) and overlapped with the control range (59.6%–84.1%; mean: 72.4%). In contrast, FOXP3 MFI was significantly lower in patient Tregs (mean: 986, range: 863–1,276) compared to controls (mean: 1,937, range: 1,089–4,132; p<0.05), another indication of quantitative Treg defects. Different patterns of FOXP3 expression have been reported, depending on the type and location of the mutation. While Treg numbers can be preserved in IPEX syndrome, FOXP3 protein expression per cell is consistently and significantly reduced. This defect in the expression level of FOXP3 likely underlies Treg dysfunction and disease pathogenesis. Assessment of FOXP3 MFI emerges as an additional valuable complementary diagnostic tool, providing functional insight beyond genetic sequencing alone. Figure 1. Clinical, immunologic, genetic, and therapeutic findings for IPEX syndrome within the CNE3i (Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação) in Brazil. (1) Demonstrates the main clinical and geographical findings of the six IPEX patients; (2) general and advanced laboratory findings; and (3) genetics and therapeutics. SP, São Paulo; MG, Minas Gerais; PE, Pernambuco; DF, Distrito Federal; ES, Espírito Santo; IgE, immunoglobulin E; IgG immunoglobulin G; DNT, double negative T cells; IFN-SG, interferon-stimulated genes; MFI, median fluorescence intensity; BMT, bone marrow transplantation; GT, gene therapy; LFW, last follow-up. FINEP funding: 0956/24; FAPESP funding: 2023/09965-0; Instituto de Investigação em Imunologia funding CNPQ/MCTI: 408685/2024-7.
2026-03-19 | Limosilactobacillus reuteri alleviates proinflammatory T-cell-mediated liver injury and transcriptomic changes in immunocompromised mice.
A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication. To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were adoptively transferred by intraperitoneal (IP) injection into lymphocyte-deficient Recombination-Activating Gene (RAG)-1-deficient (RAG1KO) mice. Liver histological inflammation and macrophages (MΦs), liver sample transcriptomes by RNAseq, and stool microbiota by 16S rRNA sequencing were then assessed in RAG1KO mice. Prob-SF-CD4+ T cells reduced the incidence and severity of liver inflammation and F4/80+MΦ infiltration by SF-CD4+ T-cell transfer. SF-CD4+ T cells upregulated genes and altered RNA splicing factors and events involved in inflammatory pathways, including Toll-like receptor (TLR) cascades, inflammatory cytokines, and death receptor signals. SF-CD4+ T cells downregulated genes linked to metabolism, including mitochondrial function, the TCA cycle, lipids, and liver detoxification. Prob-CD4+ T-cell transfer reversed SF-CD4+ T-cell-induced gene changes in inflammatory and metabolic interactive clusters while modulating distinct genes involved in TLR regulation and the cell cycle. CD4+ T-cell transfer altered gut microbial diversity compared with RAG1KO mice without CD4+ T-cell transfer. Prob-SF-CD4+ T-cell transfer exclusively increased the relative abundance (RA) of Incertae_sedis and reduced the RA of Clostridia_vadinBB60_group in the stool of RAG1KO mice. Inflammatory lymphocytes (CD4+ T cells) can perpetuate an exaggerated immune response in an immunologically naïve host. Feeding with DSM 17938 modulated T cells and allowed them to provide beneficial effects to the recipient. We observed activation of multiple genes and their interactions. These findings suggest that probiotics or probiotic-modulated T cells could be further explored as therapeutic options for autoimmune liver diseases.
2026-07-28 | Limosilactobacillus reuteri-educated T cells protect against activation of liver inflammation in immunocompromised mice 2229185
Abstract Introduction Oral administration of probiotic Limosilactobacillus reuteri DSM 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in Treg-deficient scurfy (SF) mice, which model human IPEX syndrome. It is unclear how DSM 17938 educated SF-CD4+T cells can facilitate T cell-liver communication. Methods We adoptively transferred by intraperitoneal injection cells isolated from SF spleens into lymphocyte-deficient-RAG1KO mice and compared the CD4+T cells from SF mice gavage-fed with DSM 17938 with the CD4+T cells from untreated SF mice (Prob-SF-CD4+T cells versus SF-CD4+T cells). Liver inflammatory histology and transcriptomes in RAG1KO mice were analyzed. Results We observed that Prob-SF-CD4+T cells reduced the incidence and severity of liver inflammation caused by transferring SF-CD4+T cells. SF-CD4+T cells up-regulated expression of liver genes involved in TLR cascades, inflammatory cytokine and death receptor signals, while down-regulated genes linked to mitochondrial respiratory chain complexes, TCA cycle, liver detoxification and lipid metabolism. However, Prob-SF-CD4+T cell transfer reversed SF-CD4+T cell-induced transcriptomic changes in inflammatory and metabolic clusters by modulating distinct genes participating in TLR regulation, mitochondrial function and cell cycle. Conclusion In conclusion, inflammatory CD4+T cells can perpetuate an exaggerated immune response in the immunologically naïve host. DSM17938 has the capacity to reprogram inflammatory CD4+T cells and allowed them to benefit the recipient. Probiotic-modulated T cells can be further explored as a therapeutic option for autoimmune liver diseases. Funding Source National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) R03AI153725 Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-28 | Targeting the FOXP3—T-bet interaction to restore Treg stability in IFN-γ—driven autoimmunity 2254306
Abstract Introduction Regulatory T cells (Tregs) maintain immune homeostasis through FOXP3-centered transcriptional complexes that tightly control lineage stability and suppressive function. However, how specific FOXP3 mutations disturb this complex and drive pathogenic Treg reprogramming in IPEX syndrome remains unclear. We identified a distinctive mechanism by which the FOXP3 V408M mutation promotes Th1-skewed inflammation and also explored a pharmacological strategy to restore Treg stability. Methods We generated FOXP3 V408M knock-in mice and performed immunophenotyping, transcriptomic, and chromatin conformation analyses to determine how the mutation affects FOXP3—T-bet interaction and Ifng transcription. An AI-driven virtual screening strategy integrating sequence- and structure-based modeling was applied to identify compounds that stabilize FOXP3—T-bet interaction. Functional validation was performed in vitro and in multiple in vivo mouse models. Results FOXP3 V408M mutation disrupted the FOXP3—T-bet interaction, thereby releasing T-bet from FOXP3-mediated repression and enhancing Ifng transcription. This defect reprogrammed Tregs toward an IFN-γ—producing phenotype that promoted Th1 inflammation. Among the AI-driven screening hits, 430C10 emerged as a first-in-class FOXP3-targeting stabilizer binding an allosteric pocket within the FKH domain. 430C10 reinforced the FOXP3—T-bet interaction and suppressed T-bet—driven IFN-γ production by Tregs. Oral 430C10 treatment markedly alleviated IFN-γ+ Treg—driven inflammation in FOXP3 V408M mice and improved disease outcomes in an acute colitis model under FOXP3 WT settings. Conclusion Our findings define the FOXP3—T-bet interaction as a tunable checkpoint controlling Treg stability and IFN-γ—driven autoimmunity. Pharmacological stabilization of this interaction with 430C10 provides a proof-of-concept therapeutic strategy for restoring immune homeostasis in IPEX syndrome and related autoimmune diseases. Funding Source Our research is supported by National Natural Science Foundation of China (82271829, 32130041, 82441047, 82241222); The Innovation Program of Shanghai Municipal Education Commission (21140902900); Noncommunicable Chronic Diseases-National Science and Tech Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-06-26 | FOXP3 Mutations and Instability as Determinants of Regulatory T-Cell Plasticity in Endocrine Autoimmunity
Autoimmune endocrine diseases constitute a group of disorders characterized by immune-mediated destruction or dysfunction of hormone-producing glands. The pathogenesis of these diseases reflects a breakdown of immune tolerance in which regulatory T cells (Tregs) play a key role. The transcription factor forkhead box P3 (FOXP3) is a master regulator of Treg differentiation and suppressive function. Also, it is central to maintaining self-tolerance. Genetic mutations in FOXP3, including those responsible for immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, highlight the critical role of FOXP3 in endocrine immune tolerance. Emerging evidence suggests that autoimmune endocrine disorders may reflect organ-specific destabilization of FOXP3 expression rather than complete Treg deficiency. The reversibility or irreversible loss of FOXP3 gene expression represents a key determinant of Treg plasticity and the persistence of autoimmune inflammation. This review proposes an integrated genetic–epigenetic model of FOXP3 instability and examines how the endocrine microenvironment shapes Treg plasticity. Genetic or epigenetic alterations affecting FOXP3 expression can impair Treg activity and precipitate endocrine organ-specific autoimmunity. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA-mediated regulation that modulate FOXP3 transcriptional activity are discussed. From a translational perspective, the potential of FOXP3 as a biomarker for endocrine disease susceptibility and progression was summarized. Furthermore, therapeutic strategies employed for expanding or engineering functional FOXP3+ Tregs using antigen-specific vaccines, chimeric antigen receptors (CAR)-Tregs, gene therapy, or low-dose interleukin-2 (IL-2) were described.
2026-05-01 | Peripheral Expression of FOXP3 in Brazilian Patients with IPEX Syndrome: From FOXP3 Biomarker to Targeted FOXP3 Therapy Within the CNE3I
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder caused by loss-of-function mutations in the FOXP3 gene, which is critical for the development of functional regulatory T cells (Tregs). In IPEX patients, Tregs are unable to inhibit effector T cell proliferation and cytokine production, leading to a loss of peripheral immune tolerance. The disease presents with heterogeneous clinical manifestations, severe early-onset autoimmunity, the classic triad (enteropathy, eczema, and type 1 diabetes), as well as atypical or late-onset symptoms. A clear genotype–phenotype correlation has not been established for IPEX, and immunological assessments that could contribute to the diagnosis are scarce. Therefore, we aim to characterize the peripheral Treg cells in IPEX patients in Brazil through combined quantitative and qualitative flow cytometry analysis. We enrolled 6 male patients with a confirmed IPEX diagnosis (clinical, genetic, and immunological). All patients exhibited autoimmunity (enteropathy: 5/6; arthritis: 3/6; hemolytic anemia: 2/6; type 1 diabetes: 2/6), and allergic manifestations (rhinitis: 6/6; asthma: 4/6), eczema (4/6), and recurrent sinusitis (4/6) were also observed. Up to the last follow-up, two patients were alive after bone marrow transplantation and one after gene therapy (Figure 1). Peripheral FOXP3 expression was assessed in peripheral blood mononuclear cells (PBMCs) by flow cytometry (CD3, CD4, CD25, CD127, and FOXP3). Quantitative analysis determined the frequency of Tregs (CD4+CD25+CD127-FOXP3+), while qualitative analysis measured FOXP3 protein expression via median fluorescence intensity (MFI). The frequency of circulating Tregs in IPEX patients from our cohort was highly variable (14.6%–81.2%; mean: 58.5%) and overlapped with the control range (59.6%–84.1%; mean: 72.4%). In contrast, FOXP3 MFI was significantly lower in patient Tregs (mean: 986, range: 863–1,276) compared to controls (mean: 1,937, range: 1,089–4,132; p<0.05), another indication of quantitative Treg defects. Different patterns of FOXP3 expression have been reported, depending on the type and location of the mutation. While Treg numbers can be preserved in IPEX syndrome, FOXP3 protein expression per cell is consistently and significantly reduced. This defect in the expression level of FOXP3 likely underlies Treg dysfunction and disease pathogenesis. Assessment of FOXP3 MFI emerges as an additional valuable complementary diagnostic tool, providing functional insight beyond genetic sequencing alone. Figure 1. Clinical, immunologic, genetic, and therapeutic findings for IPEX syndrome within the CNE3i (Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação) in Brazil. (1) Demonstrates the main clinical and geographical findings of the six IPEX patients; (2) general and advanced laboratory findings; and (3) genetics and therapeutics. SP, São Paulo; MG, Minas Gerais; PE, Pernambuco; DF, Distrito Federal; ES, Espírito Santo; IgE, immunoglobulin E; IgG immunoglobulin G; DNT, double negative T cells; IFN-SG, interferon-stimulated genes; MFI, median fluorescence intensity; BMT, bone marrow transplantation; GT, gene therapy; LFW, last follow-up. FINEP funding: 0956/24; FAPESP funding: 2023/09965-0; Instituto de Investigação em Imunologia funding CNPQ/MCTI: 408685/2024-7.
2026-03-19 | Limosilactobacillus reuteri alleviates proinflammatory T-cell-mediated liver injury and transcriptomic changes in immunocompromised mice.
A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication. To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were adoptively transferred by intraperitoneal (IP) injection into lymphocyte-deficient Recombination-Activating Gene (RAG)-1-deficient (RAG1KO) mice. Liver histological inflammation and macrophages (MΦs), liver sample transcriptomes by RNAseq, and stool microbiota by 16S rRNA sequencing were then assessed in RAG1KO mice. Prob-SF-CD4+ T cells reduced the incidence and severity of liver inflammation and F4/80+MΦ infiltration by SF-CD4+ T-cell transfer. SF-CD4+ T cells upregulated genes and altered RNA splicing factors and events involved in inflammatory pathways, including Toll-like receptor (TLR) cascades, inflammatory cytokines, and death receptor signals. SF-CD4+ T cells downregulated genes linked to metabolism, including mitochondrial function, the TCA cycle, lipids, and liver detoxification. Prob-CD4+ T-cell transfer reversed SF-CD4+ T-cell-induced gene changes in inflammatory and metabolic interactive clusters while modulating distinct genes involved in TLR regulation and the cell cycle. CD4+ T-cell transfer altered gut microbial diversity compared with RAG1KO mice without CD4+ T-cell transfer. Prob-SF-CD4+ T-cell transfer exclusively increased the relative abundance (RA) of Incertae_sedis and reduced the RA of Clostridia_vadinBB60_group in the stool of RAG1KO mice. Inflammatory lymphocytes (CD4+ T cells) can perpetuate an exaggerated immune response in an immunologically naïve host. Feeding with DSM 17938 modulated T cells and allowed them to provide beneficial effects to the recipient. We observed activation of multiple genes and their interactions. These findings suggest that probiotics or probiotic-modulated T cells could be further explored as therapeutic options for autoimmune liver diseases.
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Drug Discovery Landscape
2 orphan drug designations for Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.
2 orphan drug designations for Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
autologous CD34+ hematopoietic stem and progenitor cells modified ex-vivo with a lentiviral vector which restores endogenously regulated expression of FOXP3 | cell therapies | FDA | 2021-04-27 | — | ImmunoVec |
autologous patients¿ CD4+ T cells that have been subjected to lentivirus mediated gene transfer of healthy FOXP3 | gene therapies | FDA | 2020-10-26 | — | Stanford University |
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