Fecal IgA Levels and Gut Microbiota Composition Are Regulated by Invariant Natural Killer T Cells

Author(s):Show less -

de Aguiar, Cristhiane Favero ^{[1, 2]} ; Castoldi, Angela ^[1] ; Amano, Mariane T. ^{[1, 3]} ; Ignacio, Aline ^[1] ; Terra, Fernanda Fernandes ^[1] ; Cruz, Mario ^[1] ; Felizardo, Raphael J. F. ^[4] ; Braga, Tarcio Teodoro ^[1] ; Davanzo, Gustavo Gastao ^[2] ; Gambarini, Victor ^[2] ; Antonio, Tiago ^[1] ; Brasil Antiorio, Ana Tada Fonseca ^[2] ; Hiyane, Meire Ioshie ^[1] ; da Fonseca, Denise Morais ^[1] ; Andrade-Oliveira, Vinicius ^{[5, 1]} ; Saraiva Camara, Niels Olsen ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Av Prof Linen Prestes, 1730-2 Andar, Sala 238, BR-0550890 Sao Paulo, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

^[3] Hosp Sirio Libanes, Inst Sirio Libanes Ensino & Pesquisa, Sao Paulo, SP - Brazil

^[4] Fed Univ Sao Paulo UNIFESP, Dept Med, Div Nephrol, Sao Paulo, SP - Brazil

^[5] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: INFLAMMATORY BOWEL DISEASES; v. 26, n. 5, p. 697-708, MAY 2020.
• Web of Science Citations: 0

Abstract

Background: The gut microbiota is a key element to support host homeostasis and the development of the immune system. The relationship between the microbiota and immunity is a 2-way road, in which the microbiota contributes to the development/function of immune cells and immunity can affect the composition of microbes. In this context, natural killer T cells (NKT cells) are distinct T lymphocytes that play a role in gut immunity and are influenced by gut microbes. In our work, we investigated the involvement of invariant NKT cells (iNKT) in intestinal homeostasis. Results: We found that iNKT-deficient mice (iNKT-KO) had reduced levels of fecal IgA and an altered composition of the gut microbiota, with increased Bacteroidetes. The absence of iNKT cells also affected TGF-beta 1 levels and plasma cells, which were significantly reduced in knockout (KO) mice. In addition, when submitted to dextran sodium sulfate colitis, iNKT-KO mice had worsening of colitis when compared with wild-type (WT) mice. To further address iNKT cell contribution to intestinal homeostasis, we adoptively transferred iNKT cells to KO mice, and they were submitted to colitis. Transfer of iNKT cells improved colitis and restored fecal IgA levels and gut microbiota. Conclusions: Our results indicate that intestinal NKT cells are important modulators of intestinal homeostasis and that gut microbiota composition may be a potential target in the management of inflammatory bowel diseases. (AU)

• FAPESP's process: 12/16794-3 - Influence of gut microbiota on NKT cells profile in an experimental model of colitis
• Grantee: Cristhiane Favero de Aguiar
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/12848-5 - Studying NKT cell metabolism in obesity and metabolic syndrome
• Grantee: Cristhiane Favero de Aguiar
• Support Opportunities: Scholarships in Brazil - Post-Doctoral