NK1.1⁻CD4⁺NKG2D⁺ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

Abstract

CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN‐γ and TNF‐α to promote inflammation, but others produce TGF‐β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1− CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1− CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS‐induced colitis. NK1.1− CD4+ NKG2D+ cells expressed TGF‐β and FasL without secreting IFN‐γ, IL‐21 and IL‐17 and displayed no cytotoxicity. The adoptive transfer of NK1.1− CD4+ NKG2D+ cells suppressed DSS‐induced colitis largely dependent on TGF‐β. NK1.1− CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG‐3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1− CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA‐3 and ROR‐γt. Thus, NK1.1− CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

“…IF and WB analyses were carried out as previously described [ 22 , 23 ]. Briefly, for IF analysis, slides were incubated overnight at 4°C in a humid chamber with an antibody against MPO (1 : 500 dilution), CD68 (1 : 200 dilution), claudin-1 (1 : 200 dilution), occludin (1 : 200 dilution), ZO-1 (1 : 200 dilution), and NLRP3 (1 : 200 dilution) and then incubated by biotinylated secondary antibody (1 : 500 dilution) for 60 minutes.…”

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

“…NK1.1 − NKG2D + CD4 + T cells delayed the onset of DSS-induced colitis, and their protective effect was dependent on transforming growth factor beta (TGF-β). In contrast, NK1.1 + NKG2D + CD4 + T cells exacerbated the outcome of colitis [112]. Hosomi found that the deletion of the X-box binding protein 1 (Xbp1) gene in intestinal epithelial cells led to the increased expression of ULBP and spontaneous enteritis in mice, while blocking NKG2D inhibited the cytolysis of endoplasmic reticulum (ER) pressurized epithelial cells in vitro and spontaneous enteritis in vivo [113,114].…”

The Role of Natural Killer Group 2, Member D in Chronic Inflammation and Autoimmunity

“…Using a model of dextran sulfate sodium (DSS)-induced colitis, Qian and colleagues reported perturbation of numbers and frequency of NKG2D + CD4 + and NKG2D + CD8 + T cells in colon and spleen ( 29 ). Further dissection of splenic NKG2D + CD4 + T cells according to NK1.1 expression revealed two major subsets, namely, TGF-β + FasL + T-bet + NK1.1 − cells and IFN-γ + IL-17 + IL-21 + granzymeB + perforin + T-bet − RORγt + NK1.1 + cells.…”