TIR-Domain-Containing Adapter-Inducing Interferon-β (TRIF) Regulates CXCR5+ T helper Cells in the IntestineSaravana Kanagavelu1,2, Claudia Flores1, Shinichiro Hagiwara1, Jose Ruiz1, Jinhee Hyun3, Ei E. Cho1, Frank Sun1, Laura Romero4, David Q Shih1 and Masayuki Fukata1,3,*
- *Corresponding Author:
- Masayuki Fukata
Division of Gastroenterology, Department of Medicine
F. Widjaja Foundation, Inflammatory Bowel and Immunology Research Institute
Cedars-Sinai Medical Center, 110 George Burns Road
Los Angeles, CA 90048, USA
Tel: (310) 423-0013
Fax: (310) 423-0224
E-mail: [email protected]
Received date: July 22, 2016; Accepted date: September 23, 2016; Published date: September 30, 2016
Citation: Kanagavelu S, Flores C, Hagiwara S, Ruiz J, Hyun J, et al. (2016) TIRDomain-Containing Adapter-Inducing Interferon-β (TRIF) Regulates CXCR5+T helper Cells in the Intestine. J Clin Cell Immunol 7: 458. doi:10.4172/2155-9899.1000458
Copyright: © 2016 Kanagavelu S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigenspecific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine.
Method: CD4+CXCR5+ T cells, B cells, and plasma cells in the Peyer’s patches (PPs) of WT and TRIF-deficient (TrifLPS2) mice were analyzed by flow cytometry at the baseline, 9 days post primary infection, and 7 days postsecondary infection with Y. enterocolitica. Y. enterocolitica-specific CD4+CXCR5+ T cells were generated in vitro by co-culturing peritoneal macrophages with splenic naïve T cells in the presence of Y. enterocolitica lysate. WT and TrifLPS2 mice received CD4+CXCR5+ T cells isolated either from Y. enterocolitica-primed WT mice or generated in vitro. These mice were infected with Y. enterocolitica and followed up to 4 weeks. Y. enterocolitica-specific IgA and IgG were measured in stool and serum samples, respectively.
Results: At baseline, CD4+CXCR5+ T cell proportion was higher but the proportion of B cells and plasma cells was lower in the PPs of TrifLPS2 mice compared to WT mice. After infection, the proportion of plasma cells also became higher in the PPs of TrifLPS2 mice compared to WT mice. Corresponding increase of Y. enterocolitica-specific stool IgA but not serum IgG was found in TrifLPS2 mice compared to WT mice. Both in vivo isolated and in vitro generated CD4+CXCR5+ T cells induced protective immunity against Y. enterocolitica infection.
Conclusion: Our results reveal a novel role of TRIF in the regulation of humoral immunity in the intestine that can be utilized as a basis for a unique vaccine strategy.