Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis
The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelia...
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| Autor*in: |
Efren A. Reyes [verfasserIn] David Castillo-Azofeifa [verfasserIn] Jérémie Rispal [verfasserIn] Tomas Wald [verfasserIn] Rachel K. Zwick [verfasserIn] Brisa Palikuqi [verfasserIn] Angela Mujukian [verfasserIn] Shervin Rabizadeh [verfasserIn] Alexander R. Gupta [verfasserIn] James M. Gardner [verfasserIn] Dario Boffelli [verfasserIn] Zev J. Gartner [verfasserIn] Ophir D. Klein [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: The Journal of Clinical Investigation - American Society for Clinical Investigation, 2022, 133(2023), 20 |
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| Übergeordnetes Werk: |
volume:133 ; year:2023 ; number:20 |
| Links: |
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| Katalog-ID: |
DOAJ091033187 |
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| 520 | |a The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. | ||
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(DE-627)DOAJ091033187 (DE-599)DOAJ6e8bbf33ec144be58c7912b2853fe1d7 DE-627 ger DE-627 rakwb eng Efren A. Reyes verfasserin aut Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. Gastroenterology Medicine R David Castillo-Azofeifa verfasserin aut Jérémie Rispal verfasserin aut Tomas Wald verfasserin aut Rachel K. Zwick verfasserin aut Brisa Palikuqi verfasserin aut Angela Mujukian verfasserin aut Shervin Rabizadeh verfasserin aut Alexander R. Gupta verfasserin aut James M. Gardner verfasserin aut Dario Boffelli verfasserin aut Zev J. Gartner verfasserin aut Ophir D. Klein verfasserin aut In The Journal of Clinical Investigation American Society for Clinical Investigation, 2022 133(2023), 20 (DE-627)316004677 (DE-600)2018375-6 15588238 nnns volume:133 year:2023 number:20 https://doaj.org/article/6e8bbf33ec144be58c7912b2853fe1d7 kostenfrei https://doi.org/10.1172/JCI163591 kostenfrei https://doaj.org/toc/1558-8238 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 133 2023 20 |
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(DE-627)DOAJ091033187 (DE-599)DOAJ6e8bbf33ec144be58c7912b2853fe1d7 DE-627 ger DE-627 rakwb eng Efren A. Reyes verfasserin aut Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. Gastroenterology Medicine R David Castillo-Azofeifa verfasserin aut Jérémie Rispal verfasserin aut Tomas Wald verfasserin aut Rachel K. Zwick verfasserin aut Brisa Palikuqi verfasserin aut Angela Mujukian verfasserin aut Shervin Rabizadeh verfasserin aut Alexander R. Gupta verfasserin aut James M. Gardner verfasserin aut Dario Boffelli verfasserin aut Zev J. Gartner verfasserin aut Ophir D. Klein verfasserin aut In The Journal of Clinical Investigation American Society for Clinical Investigation, 2022 133(2023), 20 (DE-627)316004677 (DE-600)2018375-6 15588238 nnns volume:133 year:2023 number:20 https://doaj.org/article/6e8bbf33ec144be58c7912b2853fe1d7 kostenfrei https://doi.org/10.1172/JCI163591 kostenfrei https://doaj.org/toc/1558-8238 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 133 2023 20 |
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(DE-627)DOAJ091033187 (DE-599)DOAJ6e8bbf33ec144be58c7912b2853fe1d7 DE-627 ger DE-627 rakwb eng Efren A. Reyes verfasserin aut Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. Gastroenterology Medicine R David Castillo-Azofeifa verfasserin aut Jérémie Rispal verfasserin aut Tomas Wald verfasserin aut Rachel K. Zwick verfasserin aut Brisa Palikuqi verfasserin aut Angela Mujukian verfasserin aut Shervin Rabizadeh verfasserin aut Alexander R. Gupta verfasserin aut James M. Gardner verfasserin aut Dario Boffelli verfasserin aut Zev J. Gartner verfasserin aut Ophir D. Klein verfasserin aut In The Journal of Clinical Investigation American Society for Clinical Investigation, 2022 133(2023), 20 (DE-627)316004677 (DE-600)2018375-6 15588238 nnns volume:133 year:2023 number:20 https://doaj.org/article/6e8bbf33ec144be58c7912b2853fe1d7 kostenfrei https://doi.org/10.1172/JCI163591 kostenfrei https://doaj.org/toc/1558-8238 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 133 2023 20 |
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(DE-627)DOAJ091033187 (DE-599)DOAJ6e8bbf33ec144be58c7912b2853fe1d7 DE-627 ger DE-627 rakwb eng Efren A. Reyes verfasserin aut Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. Gastroenterology Medicine R David Castillo-Azofeifa verfasserin aut Jérémie Rispal verfasserin aut Tomas Wald verfasserin aut Rachel K. Zwick verfasserin aut Brisa Palikuqi verfasserin aut Angela Mujukian verfasserin aut Shervin Rabizadeh verfasserin aut Alexander R. Gupta verfasserin aut James M. Gardner verfasserin aut Dario Boffelli verfasserin aut Zev J. Gartner verfasserin aut Ophir D. Klein verfasserin aut In The Journal of Clinical Investigation American Society for Clinical Investigation, 2022 133(2023), 20 (DE-627)316004677 (DE-600)2018375-6 15588238 nnns volume:133 year:2023 number:20 https://doaj.org/article/6e8bbf33ec144be58c7912b2853fe1d7 kostenfrei https://doi.org/10.1172/JCI163591 kostenfrei https://doaj.org/toc/1558-8238 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 133 2023 20 |
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(DE-627)DOAJ091033187 (DE-599)DOAJ6e8bbf33ec144be58c7912b2853fe1d7 DE-627 ger DE-627 rakwb eng Efren A. Reyes verfasserin aut Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. Gastroenterology Medicine R David Castillo-Azofeifa verfasserin aut Jérémie Rispal verfasserin aut Tomas Wald verfasserin aut Rachel K. Zwick verfasserin aut Brisa Palikuqi verfasserin aut Angela Mujukian verfasserin aut Shervin Rabizadeh verfasserin aut Alexander R. Gupta verfasserin aut James M. Gardner verfasserin aut Dario Boffelli verfasserin aut Zev J. Gartner verfasserin aut Ophir D. Klein verfasserin aut In The Journal of Clinical Investigation American Society for Clinical Investigation, 2022 133(2023), 20 (DE-627)316004677 (DE-600)2018375-6 15588238 nnns volume:133 year:2023 number:20 https://doaj.org/article/6e8bbf33ec144be58c7912b2853fe1d7 kostenfrei https://doi.org/10.1172/JCI163591 kostenfrei https://doaj.org/toc/1558-8238 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 133 2023 20 |
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The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. |
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The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. |
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The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell–derived TNF as an upstream regulator of mucin homeostasis. |
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