Regulatory T cells control Effector T cell Inflammation in Human Prediabetes

Li, Rui; Pugh, Gabriella H.; Tevonian, Erin; Thompson, Katherine; Lauffenburger, Douglas A.; Kern, Philip A.; Nikolajczyk, Barbara S.

doi:10.2337/figshare.16915180.v1

Cited by 2 publications

(3 citation statements)

References 17 publications

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“…IL‐23 and IL‐1b were lesser contributors to T2D‐specific inflammation (components 2 and 3, respectively; Figure 1G). We conclude, from both CD3/CD28‐ and LPS‐elicited profiles, that metabolic status impacts cytokine competency in cells from donors with obesity, consistent with our work on purified CD4 + T cells [30].…”

Section: Resultssupporting

confidence: 89%

“…Responses to T cell‐targeted CD3/CD28 underscored the distinctiveness of preT2D inflammation first indicated by our analysis of cytokine competency of purified CD4 + T cells [30] and significantly extends existing analyses of cytokines in preT2D plasma/serum [39, 40]. The acute myeloid response, combined with the more sustained response to CD3/CD28 that dominates overall “inflammation” at 72 hours, is consistent with a canonical immune response in which innate immune cells respond quickly to prime a sustained adaptive immune response.…”

Section: Discussionmentioning

confidence: 87%

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T cells dominate peripheral inflammation in a cross‐sectional analysis of obesity‐associated diabetes

Pugh

Calvo

Agrawal

et al. 2022

Obesity

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Objective Myeloid cells dominate metabolic disease‐associated inflammation (metaflammation) in mouse obesity, but the contributions of myeloid cells to the peripheral inflammation that fuels sequelae of human obesity are untested. This study used unbiased approaches to rank contributions of myeloid and T cells to peripheral inflammation in people with obesity across the spectrum of metabolic health. Methods Peripheral blood mononuclear cells (PBMCs) from people with obesity with or without prediabetes or type 2 diabetes were stimulated with T cell‐targeting CD3/CD28 or myeloid‐targeting lipopolysaccharide for 20 to 72 hours to assess cytokine production using Bio‐Plex. Bioinformatic modeling ranked cytokines with respect to their predictive power for metabolic health. Intracellular tumor necrosis factor α was quantitated as a classical indicator of metaflammation. Results Cytokines increased over 72 hours following T cell‐, but not myeloid‐, targeted stimulation to indicate that acute myeloid inflammation may shift to T cell inflammation over time. T cells contributed more tumor necrosis factor α to peripheral inflammation regardless of metabolic status. Bioinformatic combination of cytokines from all cohorts, stimuli, and time points indicated that T cell‐targeted stimulation was most important for differentiating inflammation in diabetes, consistent with previous identification of a mixed T helper type 1/T helper type 17 cytokine profile in diabetes. Conclusions T cells dominate peripheral inflammation in obesity; therefore, targeting T cells may be an effective approach for prevention/management of metaflammation.

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