Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+T cells. Science 2017, pii: eaah5825.

報告日期: 2017/10/24
報告時間: 17:10/18:00
報告學生: 陳佩琪
講評老師: 徐麗君
附件下載: 下載[1663-1506044876-1.pdf] 

Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells

Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S, Cella M, Gordon JI, Hsieh CS, Colonna M.,Science. (2017) 357(6353):806-810.

Speaker: Pei-Chi Chen (陳佩琪)                    Time : 17:10~18:00, Oct.24, 2017

Commentator: Dr. Li-Jin Hsu (徐麗君)    Place: Room 602

How the microbiota affects health and disease becomes a crucial question recently. Because human intestine harbors numbers of commensal bacteria and encounters daily food antigens, mucosal tolerance was generated to prevent unnecessary inflammation. One of immunosuppressive mediators is CD4+CD8αα+ double-positive intraepithelial T lymphocytes (DP IELs), which derives from CD4+ T cells through downregulation of the transcription factor ThPOK. Last year, scientists had found that DP IELs are absent in germ-free (GM) mice [1]. It seems that the microbiota plays a critical role in DP IELs developments. However, seldom research demonstrated the detail mechanism of how the microbiota regulates the differentiation of these cells. In the beginning, the authors found that DP IELs numbers in mice varied in different vivaria. After sequencing 16S ribosomal RNA genes from the microbiota of candidate mice, they revealed that Lactobacillus reuteri induced DP IELs developments. Furthermore, although TCR αβ repertoires analysis indicated L. reuteri did not shape DP IELs differentiation by inducing specific Vα and Vβ usages, HPLC-MS chromatography analyzed L. reuteri PT-P (tryptophan containing medium) cultured supernatant showed that this bacteria generated indole derivatives of tryptophan, ILA (indole-3-lactic acid), an aryl-hydrocarbon receptor (AhR) ligand. Following experiments demonstrated that ILA activated AhR signaling in CD4+ T cells and led to the down-regulation of ThPOK and drive CD4+ T cell toward DP IEL fate. In conclusion, the authors proved that L. reuteri promotes tryptophan catabolism and actives AhR signaling to reprogram CD4 IELs toward DP IELs. This finding may provide a basis for the combination of L. reuteri and tryptophan-rich diet to maintain the mucosal homeostasis that is modifiable by DP IELs [2].

References

  1. Sujino T, London M, Hoytema van Konijnenburg DP, Rendon T, Buch T, Silva HM, Lafaille JJ, Reis BS, Mucida D, Tissue adaptation of regulatory and intraepithelial CD4⁺ T cells controls gut inflammation. Science. (2016) 352(6293):1581-6.
  2. Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quévrain E, Bridonneau C, Preisser L, Asehnoune K, Labarrière N, Altare F, Sokol H, Jotereau F., CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.
  3. PLoS Biol. (2014) 12(4):e1001833.