---
OA_place: publisher
OA_type: hybrid
_id: '19928'
abstract:
- lang: eng
  text: 'Patho-mechanistic origins of ulcerative colitis are still poorly understood.
    The actin cross-linker filamin A (FLNA) impacts cellular responses through interaction
    with cytosolic proteins. Posttranscriptional A-to-I editing generates two forms
    of FLNA: genome-encoded FLNAQ and FLNAR. FLNA is edited in colon fibroblasts,
    smooth muscle cells, and endothelial cells. We found that the FLNA editing status
    determines colitis severity. Editing was highest in healthy colons and reduced
    during murine and human colitis. Mice that exclusively express FLNAR were highly
    resistant to DSS-induced colitis, whereas fully FLNAQ animals developed severe
    inflammation. While the genetic induction of FLNA editing influenced transcriptional
    states of structural cells and microbiome composition, we found that FLNAR exerts
    protection specifically via myeloid cells, which are physiologically unedited.
    Introducing fixed FLNAR did not hamper cell migration but reduced macrophage inflammation
    and rendered neutrophils less prone to NETosis. Thus, loss of FLNA editing correlates
    with colitis severity, and targeted editing of myeloid cells serves as a novel
    therapeutic approach in intestinal inflammation.'
acknowledgement: "Sequencing was performed by the Vienna BioCenter Core Facilities
  (Medical University of Vienna Core Facility) and the Biomedical Sequencing Facility
  at CeMM, Vienna. Cell sorting and flow cytometry were performed at the Core Facility
  Flow Cytometry and Imaging (Medical University of Vienna). We thank Jasmin Schwarz,
  Gudrun Kohl, Petra Pjevac, and Joana Seneca Silva from the Joint Microbiome Facility
  of the Medical University of Vienna and the University of Vienna for assisting with
  amplicon and metagenomic sequencing, as well as repositing of sequencing data. We
  thank Sophia Derdak and Michael Schuster for initial data analysis, Robert Vilvoi
  and Stephan Hemm for animal handling, Marcel Kertesz for mouse genotyping, and Salwan
  Roumaia for next generation sequencing sample preparation. Treatment schemes and
  graphical abstracts were created with https://BioRender.com.\r\n\r\nThis work was
  supported by the Austrian Science Fund, grant number ZK 57-B28 to C. Vesely, R.
  Gawish, and F.C. Pereira; grant number V 1025-B to R. Gawish; grant number DOC32-B28
  to R. Varada and M.F. Jantsch; and F8007 and P32678 to M.F. Jantsch. Open Access
  funding provided by Medical University of Vienna."
article_number: e20240109
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Riem
  full_name: Gawish, Riem
  last_name: Gawish
- first_name: Rajagopal
  full_name: Varada, Rajagopal
  last_name: Varada
- first_name: Florian
  full_name: Deckert, Florian
  last_name: Deckert
- first_name: Anastasiya
  full_name: Hladik, Anastasiya
  last_name: Hladik
- first_name: Linda
  full_name: Steinbichl, Linda
  last_name: Steinbichl
- first_name: Laura
  full_name: Cimatti, Laura
  last_name: Cimatti
- first_name: Katarina
  full_name: Milanovic, Katarina
  last_name: Milanovic
- first_name: Mamta
  full_name: Jain, Mamta
  last_name: Jain
- first_name: Natalya
  full_name: Torgasheva, Natalya
  last_name: Torgasheva
- first_name: Andrea
  full_name: Tanzer, Andrea
  last_name: Tanzer
- first_name: Kim
  full_name: De Paepe, Kim
  last_name: De Paepe
- first_name: Tom
  full_name: Van De Wiele, Tom
  last_name: Van De Wiele
- first_name: Bela
  full_name: Hausmann, Bela
  last_name: Hausmann
- first_name: Michaela
  full_name: Lang, Michaela
  last_name: Lang
- first_name: Martin
  full_name: Pechhacker, Martin
  last_name: Pechhacker
- first_name: Nahla
  full_name: Ibrahim, Nahla
  last_name: Ibrahim
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Christine
  full_name: Brostjan, Christine
  last_name: Brostjan
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Christoph
  full_name: Gasche, Christoph
  last_name: Gasche
- first_name: Louis
  full_name: Boon, Louis
  last_name: Boon
- first_name: David
  full_name: Berry, David
  last_name: Berry
- first_name: Michael F.
  full_name: Jantsch, Michael F.
  last_name: Jantsch
- first_name: Fatima C.
  full_name: Pereira, Fatima C.
  last_name: Pereira
- first_name: Cornelia
  full_name: Vesely, Cornelia
  last_name: Vesely
citation:
  ama: Gawish R, Varada R, Deckert F, et al. Filamin A editing in myeloid cells reduces
    intestinal inflammation and protects from colitis. <i>Journal of Experimental
    Medicine</i>. 2025;222(9). doi:<a href="https://doi.org/10.1084/jem.20240109">10.1084/jem.20240109</a>
  apa: Gawish, R., Varada, R., Deckert, F., Hladik, A., Steinbichl, L., Cimatti, L.,
    … Vesely, C. (2025). Filamin A editing in myeloid cells reduces intestinal inflammation
    and protects from colitis. <i>Journal of Experimental Medicine</i>. Rockefeller
    University Press. <a href="https://doi.org/10.1084/jem.20240109">https://doi.org/10.1084/jem.20240109</a>
  chicago: Gawish, Riem, Rajagopal Varada, Florian Deckert, Anastasiya Hladik, Linda
    Steinbichl, Laura Cimatti, Katarina Milanovic, et al. “Filamin A Editing in Myeloid
    Cells Reduces Intestinal Inflammation and Protects from Colitis.” <i>Journal of
    Experimental Medicine</i>. Rockefeller University Press, 2025. <a href="https://doi.org/10.1084/jem.20240109">https://doi.org/10.1084/jem.20240109</a>.
  ieee: R. Gawish <i>et al.</i>, “Filamin A editing in myeloid cells reduces intestinal
    inflammation and protects from colitis,” <i>Journal of Experimental Medicine</i>,
    vol. 222, no. 9. Rockefeller University Press, 2025.
  ista: Gawish R, Varada R, Deckert F, Hladik A, Steinbichl L, Cimatti L, Milanovic
    K, Jain M, Torgasheva N, Tanzer A, De Paepe K, Van De Wiele T, Hausmann B, Lang
    M, Pechhacker M, Ibrahim N, de Vries I, Brostjan C, Sixt MK, Gasche C, Boon L,
    Berry D, Jantsch MF, Pereira FC, Vesely C. 2025. Filamin A editing in myeloid
    cells reduces intestinal inflammation and protects from colitis. Journal of Experimental
    Medicine. 222(9), e20240109.
  mla: Gawish, Riem, et al. “Filamin A Editing in Myeloid Cells Reduces Intestinal
    Inflammation and Protects from Colitis.” <i>Journal of Experimental Medicine</i>,
    vol. 222, no. 9, e20240109, Rockefeller University Press, 2025, doi:<a href="https://doi.org/10.1084/jem.20240109">10.1084/jem.20240109</a>.
  short: R. Gawish, R. Varada, F. Deckert, A. Hladik, L. Steinbichl, L. Cimatti, K.
    Milanovic, M. Jain, N. Torgasheva, A. Tanzer, K. De Paepe, T. Van De Wiele, B.
    Hausmann, M. Lang, M. Pechhacker, N. Ibrahim, I. de Vries, C. Brostjan, M.K. Sixt,
    C. Gasche, L. Boon, D. Berry, M.F. Jantsch, F.C. Pereira, C. Vesely, Journal of
    Experimental Medicine 222 (2025).
date_created: 2025-06-29T22:01:15Z
date_published: 2025-09-01T00:00:00Z
date_updated: 2025-12-30T09:00:42Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1084/jem.20240109
external_id:
  isi:
  - '001502896900001'
  pmid:
  - '40471139'
file:
- access_level: open_access
  checksum: 708d61fb8cf1d83ee1e33ddcfde0857e
  content_type: application/pdf
  creator: dernst
  date_created: 2025-12-30T09:00:04Z
  date_updated: 2025-12-30T09:00:04Z
  file_id: '20899'
  file_name: 2025_JEM_Gawish.pdf
  file_size: 9349311
  relation: main_file
  success: 1
file_date_updated: 2025-12-30T09:00:04Z
has_accepted_license: '1'
intvolume: '       222'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Experimental Medicine
publication_identifier:
  eissn:
  - 1540-9538
  issn:
  - 0022-1007
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Filamin A editing in myeloid cells reduces intestinal inflammation and protects
  from colitis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 222
year: '2025'
...
---
_id: '6497'
abstract:
- lang: eng
  text: T cells are actively scanning pMHC-presenting cells in lymphoid organs and
    nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the
    T cell actomyosin cytoskeleton facilitates this task in distinct environments
    is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative
    regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface
    stiffness in primary T cells. Nonetheless, intravital imaging revealed robust
    motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and
    differentiation during immune responses. In contrast, accumulation of Myo9b−/−
    CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for
    T cell crossing of basement membranes, such as those which are present between
    dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control
    of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell
    adaptation from lymphoid to NLT surveillance and the establishment of protective
    tissue–resident T cell populations.
article_processing_charge: No
author:
- first_name: Federica
  full_name: Moalli, Federica
  last_name: Moalli
- first_name: Xenia
  full_name: Ficht, Xenia
  last_name: Ficht
- first_name: Philipp
  full_name: Germann, Philipp
  last_name: Germann
- first_name: Mykhailo
  full_name: Vladymyrov, Mykhailo
  last_name: Vladymyrov
- first_name: Bettina
  full_name: Stolp, Bettina
  last_name: Stolp
- first_name: Ingrid
  full_name: de Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: de Vries
- first_name: Ruth
  full_name: Lyck, Ruth
  last_name: Lyck
- first_name: Jasmin
  full_name: Balmer, Jasmin
  last_name: Balmer
- first_name: Amleto
  full_name: Fiocchi, Amleto
  last_name: Fiocchi
- first_name: Mario
  full_name: Kreutzfeldt, Mario
  last_name: Kreutzfeldt
- first_name: Doron
  full_name: Merkler, Doron
  last_name: Merkler
- first_name: Matteo
  full_name: Iannacone, Matteo
  last_name: Iannacone
- first_name: Akitaka
  full_name: Ariga, Akitaka
  last_name: Ariga
- first_name: Michael H.
  full_name: Stoffel, Michael H.
  last_name: Stoffel
- first_name: James
  full_name: Sharpe, James
  last_name: Sharpe
- first_name: Martin
  full_name: Bähler, Martin
  last_name: Bähler
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Alba
  full_name: Diz-Muñoz, Alba
  last_name: Diz-Muñoz
- first_name: Jens V.
  full_name: Stein, Jens V.
  last_name: Stein
citation:
  ama: Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid
    tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>.
    2018;2015(7):1869–1890. doi:<a href="https://doi.org/10.1084/jem.20170896">10.1084/jem.20170896</a>
  apa: Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I.,
    … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue
    seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>.
    Rockefeller University Press. <a href="https://doi.org/10.1084/jem.20170896">https://doi.org/10.1084/jem.20170896</a>
  chicago: Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina
    Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables
    Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental
    Medicine</i>. Rockefeller University Press, 2018. <a href="https://doi.org/10.1084/jem.20170896">https://doi.org/10.1084/jem.20170896</a>.
  ieee: F. Moalli <i>et al.</i>, “The Rho regulator Myosin IXb enables nonlymphoid
    tissue seeding of protective CD8+T cells,” <i>The Journal of Experimental Medicine</i>,
    vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.
  ista: Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer
    J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe
    J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb
    enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental
    Medicine. 2015(7), 1869–1890.
  mla: Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid
    Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>,
    vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:<a href="https://doi.org/10.1084/jem.20170896">10.1084/jem.20170896</a>.
  short: F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R.
    Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga,
    M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal
    of Experimental Medicine 2015 (2018) 1869–1890.
date_created: 2019-05-28T12:36:47Z
date_published: 2018-06-06T00:00:00Z
date_updated: 2023-09-19T14:52:08Z
day: '06'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1084/jem.20170896
external_id:
  isi:
  - '000440822900011'
file:
- access_level: open_access
  checksum: 86ae5331f9bfced9a6358a790a04bef4
  content_type: application/pdf
  creator: kschuh
  date_created: 2019-05-28T12:40:05Z
  date_updated: 2020-07-14T12:47:32Z
  file_id: '6498'
  file_name: 2018_rupress_Moalli.pdf
  file_size: 3841660
  relation: main_file
file_date_updated: 2020-07-14T12:47:32Z
has_accepted_license: '1'
intvolume: '      2015'
isi: 1
issue: '7'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '06'
oa: 1
oa_version: Published Version
page: 1869–1890
publication: The Journal of Experimental Medicine
publication_identifier:
  eissn:
  - 1540-9538
  issn:
  - 0022-1007
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective
  CD8+T cells
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2015
year: '2018'
...