BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology
Abstract Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuo...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202206692 |
| _version_ | 1797663876867686400 |
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| author | Achia Khatun Xiaopeng Wu Fu Qi Kexin Gai Arjun Kharel Matthew R. Kudek Lisa Fraser Ashley Ceicko Moujtaba Y. Kasmani Amber Majnik Robert Burns Yi‐Guang Chen Nita Salzman Elizabeth J. Taparowsky Dayu Fang Calvin B. Williams Weiguo Cui |
| author_facet | Achia Khatun Xiaopeng Wu Fu Qi Kexin Gai Arjun Kharel Matthew R. Kudek Lisa Fraser Ashley Ceicko Moujtaba Y. Kasmani Amber Majnik Robert Burns Yi‐Guang Chen Nita Salzman Elizabeth J. Taparowsky Dayu Fang Calvin B. Williams Weiguo Cui |
| author_sort | Achia Khatun |
| collection | DOAJ |
| description | Abstract Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuous T cell receptor (TCR) signaling plays a vital role in the differentiation of aTregs from their resting state, and in their immune homeostasis. The process by which Tregs differentiate, adapt tissue specificity, and maintain stable phenotypic expression at the transcriptional level is still inconclusivei. In this work, the role of BATF is investigated, which is induced in response to TCR stimulation in naïve T cells and during aTreg differentiation. Mice lacking BATF in Tregs developed multiorgan autoimmune pathology. As a transcriptional regulator, BATF is required for Treg differentiation, homeostasis, and stabilization of FOXP3 expression in different lymphoid and non‐lymphoid tissues. Epigenetically, BATF showed direct regulation of Treg‐specific genes involved in differentiation, maturation, and tissue accumulation. Most importantly, FOXP3 expression and Treg stability require continuous BATF expression in Tregs, as it regulates demethylation and accessibility of the CNS2 region of the Foxp3 locus. Considering its role in Treg stability, BATF should be considered an important therapeutic target in autoimmune disease. |
| first_indexed | 2024-03-11T19:22:09Z |
| format | Article |
| id | doaj.art-786eb5c93e3443a6b323cd0698684eb8 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T19:22:09Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-786eb5c93e3443a6b323cd0698684eb82023-10-07T03:51:50ZengWileyAdvanced Science2198-38442023-10-011028n/an/a10.1002/advs.202206692BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune PathologyAchia Khatun0Xiaopeng Wu1Fu Qi2Kexin Gai3Arjun Kharel4Matthew R. Kudek5Lisa Fraser6Ashley Ceicko7Moujtaba Y. Kasmani8Amber Majnik9Robert Burns10Yi‐Guang Chen11Nita Salzman12Elizabeth J. Taparowsky13Dayu Fang14Calvin B. Williams15Weiguo Cui16Department of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USAChildren's Mercy Hospital in Kansas City 2401 Gillham Rd Kansas City MO 64108 USADepartment of Pathology Feinberg School of Medicine Northwestern University 303 E Chicago Ave Chicago IL 60611 USADepartment of Pathology Feinberg School of Medicine Northwestern University 303 E Chicago Ave Chicago IL 60611 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USAVersiti Blood Research Institute Versiti Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Biological Science Purdue University 610 Purdue Mall West Lafayette IN 47907 USADepartment of Pathology Feinberg School of Medicine Northwestern University 303 E Chicago Ave Chicago IL 60611 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USADepartment of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI 53226 USAAbstract Regulatory T (Treg) cells are inevitable to prevent deleterious immune responses to self and commensal microorganisms. Treg function requires continuous expression of the transcription factor (TF) FOXP3 and is divided into two major subsets: resting (rTregs) and activated (aTregs). Continuous T cell receptor (TCR) signaling plays a vital role in the differentiation of aTregs from their resting state, and in their immune homeostasis. The process by which Tregs differentiate, adapt tissue specificity, and maintain stable phenotypic expression at the transcriptional level is still inconclusivei. In this work, the role of BATF is investigated, which is induced in response to TCR stimulation in naïve T cells and during aTreg differentiation. Mice lacking BATF in Tregs developed multiorgan autoimmune pathology. As a transcriptional regulator, BATF is required for Treg differentiation, homeostasis, and stabilization of FOXP3 expression in different lymphoid and non‐lymphoid tissues. Epigenetically, BATF showed direct regulation of Treg‐specific genes involved in differentiation, maturation, and tissue accumulation. Most importantly, FOXP3 expression and Treg stability require continuous BATF expression in Tregs, as it regulates demethylation and accessibility of the CNS2 region of the Foxp3 locus. Considering its role in Treg stability, BATF should be considered an important therapeutic target in autoimmune disease.https://doi.org/10.1002/advs.202206692autoimmunityBATFFoxp3Treg |
| spellingShingle | Achia Khatun Xiaopeng Wu Fu Qi Kexin Gai Arjun Kharel Matthew R. Kudek Lisa Fraser Ashley Ceicko Moujtaba Y. Kasmani Amber Majnik Robert Burns Yi‐Guang Chen Nita Salzman Elizabeth J. Taparowsky Dayu Fang Calvin B. Williams Weiguo Cui BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology Advanced Science autoimmunity BATF Foxp3 Treg |
| title | BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology |
| title_full | BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology |
| title_fullStr | BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology |
| title_full_unstemmed | BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology |
| title_short | BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology |
| title_sort | batf is required for treg homeostasis and stability to prevent autoimmune pathology |
| topic | autoimmunity BATF Foxp3 Treg |
| url | https://doi.org/10.1002/advs.202206692 |
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