4.8 Article

Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C

Journal

IMMUNITY
Volume 55, Issue 4, Pages 623-+

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2022.03.009

Keywords

-

Categories

Funding

  1. National Institute of Health [R21 AI140109, R56 AI162791, R01 AI139420]
  2. National Natural Sci-ence Foundation of China [U1904132]
  3. Program for Science & Technology Innovation Talents in Higher Education of Henan Province, China [20HAS-TIT046]
  4. Natural Science Foundation of Hunan Province, China [2015JJ6072, 2020JJ4441]
  5. Research Foundation of Education Bureau of Hunan Province, China [20A304]
  6. Ministry of Science and Technol-ogy of China [2018YFA0801100]
  7. Ministry of Science and Technology of China [2021YFF0702100]
  8. National Natural Science Foundation of China [31971056]
  9. Miriam and Sheldon G. Adelson Medical Research Foundation
  10. American Heart Association Postdoc-toral Fellowship
  11. Damon Runyon Cancer Research Foundation Fellowship [DRG-2427-21]
  12. NIH [R01 DK122056, 1DP2AI136596]

Ask authors/readers for more resources

Epithelial O-GlcNAc protein modification is induced by helminth infection, promoting the transcription of key genes and secretion of cytokines involved in immune responses and mucosal barrier regulation.
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete alarmincytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available