Gab2 and Gab3 redundantly suppress colitis by modulating macrophage and CD8+ T-cell activation

Zhengqi Wang, Tamisha Y. Vaughan, Wandi Zhu, Yuhong Chen, Guoping Fu, Magdalena Medrzycki, Hikaru Nishio, Silvia T. Bunting, Pamela A. Hankey-Giblin, Asma Nusrat, Charles A. Parkos, Demin Wang, Renren Wen, Kevin D. Bunting

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Inflammatory Bowel Disease (IBD) is a multi-factorial chronic inflammation of the gastrointestinal tract prognostically linked to CD8+ T-cells, but little is known about their mechanism of activation during initiation of colitis. Here, Grb2-associated binding 2/3 adaptor protein double knockout mice (Gab2/3−/−) were generated. Gab2/3−/− mice, but not single knockout mice, developed spontaneous colitis. To analyze the cellular mechanism, reciprocal bone marrow (BM) transplantation demonstrated a Gab2/3−/− hematopoietic disease-initiating process. Adoptive transfer showed individual roles for macrophages and T-cells in promoting colitis development in vivo. In spontaneous disease, intestinal intraepithelial CD8+ but much fewer CD4+, T-cells from Gab2/3−/− mice with rectal prolapse were more proliferative. To analyze the molecular mechanism, reduced PI3-kinase/Akt/mTORC1 was observed in macrophages and T-cells, with interleukin (IL)-2 stimulated T-cells showing increased pSTAT5. These results illustrate the importance of Gab2/3 collectively in signaling responses required to control macrophage and CD8+ T-cell activation and suppress chronic colitis.

Original languageEnglish (US)
Article number486
JournalFrontiers in immunology
Issue numberMAR
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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