ISSN 1662-4009 (online)

ey0015.14-1 | Why do women have more autoimmune disease than men? | ESPEYB15

14.1 Estrogen receptor α contributes to T cell–mediated autoimmune inflammation by promoting T cell activation and proliferation

I Mohammad , I Starskaia , T Nagy , J Guo , E Yatkin , K Väänänen , WT Watford , Z Chen

To read the full abstract: Sci. Signal. 2018;11:eaap9415Women are more frequently affected by autoimmune disorders than men. A role for estrogen was suggested by the observation that the development of inflammatory bowel disease was associated with oral contraceptive use. Women also respond to infection and vaccination with higher antibody production and a T helper 2 (TH2) cell&#8211...

ey0020.8-11 | New Mechanisms | ESPEYB20

8.11. Soluble RAGE prevents type 1 diabetes expanding functional regulatory T cells

SS Leung , DJ Borg , DA McCarthy , TE Boursalian , J Cracraft , A Zhuang , AK Fotheringham , N Flemming , T Watkins , JJ Miles , PH Groop , JL Scheijen , CG Schalkwijk , RJ Steptoe , KJ Radford , M Knip , JM Forbes

Brief summary: using a murine model of diabetes and ex vivo experiments in human T-cell cultures, this study showed that short-term administration of an antagonist to the receptor for advanced glycation end products (sRAGE) modulates functional T regulatory cells (Treg) expansion and thus prevents diabetes.This study provides further support for a role of the advanced glycation end-product (AGEs)-AGE receptor (RAGE) pathways in the pathogenesis ...

ey0015.14-13 | The nature of scientific progress | ESPEYB15

14.13 Tragedy, Perseverance, and Chance - The Story of CAR-T Therapy

L Rosenbaum

To read the full abstract: N Engl J Med 2017;377:1313-1315“In 2010, 5-year-old Emily Whitehead was diagnosed with acute lymphoblastic leukemia.” So begins this remarkable story of how Emily became the first child to receive CART-19 (chimeric antigen receptor T-cell) therapy. She remains alive and well, and her successful treatment re-energised a whole line of research &#8...

ey0019.10-13 | Pathogenesis | ESPEYB19

10.13. Human islet T cells are highly reactive to preproinsulin in type 1 diabetes

AM Anderson , LG Landry , AA Alkanani , L Pyle , AC Powers , MA Atkinson , CE Mathews , BO Roep , AW Michels , M Nakayama

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2107208118. https://pubmed.ncbi.nlm.nih.gov/34611019/Brief Summary: This in vitro study explored the reactivity to preproinsulin of CD8 T cells obtained from pancreatic islets of individuals with and without type 1 diabetes (T1D). The main finding was that CD8 T cells from T1D donors were highly reactive to peptides throughout the entire prepro...

ey0016.14-4 | (1) | ESPEYB16

14.4. A reprogramming human T cell function and specificity with non-viral genome targeting

TL Roth , C Puig-Saus , R Yu , E Shifrut , J Carnevale , PJ Li , Hiatt , J Saco , P Krystofinski , H Li , V Tobin , DN Nguyen , MR Lee , AL Putnam , AL Ferris , JW Chen , JN Schickel , L Pellerin , D Carmody , G Alkorta-Aranburu , D Del Gaudio , H Matsumoto , M Morell , Y Mao , M Cho , RM Quadros , CB Gurumurthy , B Smith , M Haugwitz , SH Hughes , JS Weissman , K Schumann , JH Esensten , AP May , A Ashworth , GM Kupfer , SAW Greeley , R Bacchetta , E Meffre , MG Roncarolo , N Romberg , KC Herold , A Ribas , MD Leonetti , A Marson

To read the full abstract: Nature. 2018 Jul;559(7714):405–409This article decries a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences at specific sites in the genomes of primary human T cells, while preserving cell viability and function.The common approach to genetically...

ey0017.14-14 | (1) | ESPEYB17

14.14. T cell-mediated regulation of the microbiota protects against obesity

C Petersen , R Bell , KA Klag , S-H Lee , R Soto , A Ghazaryan , K Buhrke , HA Ekiz , KS Ost , S Boudina

To read the full abstract: Science 2019;365:eaat9351.As in humans, weight gain in mice leads to fatty liver disease, inflammatory adipose tissue, and insulin resistance. The depletion of the microbiota through antibiotic treatment rescued this weight gain. The cohousing of T-Myd88–/– mice transferred the weight gain to wild-type mice. The major feature of the microbiota formed within T-Myd88–/– mice was a reduction in Clostri...

ey0019.10-14 | Pathogenesis | ESPEYB19

10.14. An autoimmune stem-like CD8 T cell population drives type 1 diabetes

SV Gearty , F Dundar , P Zumbo , G Espinosa-Carrasco , M Shakiba , FJ Sanchez-Rivera , ND Socci , P Trivedi , SW Lowe , P Lauer , N Mohibullah , A Viale , TP DiLorenzo , D Betel , A Schietinger

Nature 2022;602(7895):156-161. https://pubmed.ncbi.nlm.nih.gov/34847567/Brief Summary: This study used a well-characterized mouse model of type 1 diabetes (T1D), the non-obese diabetic mouse (NOD), to examine the fate of CD8 T cells over the 5–30 week course of the disease. They found a stem-like autoimmune progenitor population in the pancreatic draining lymph nodes, which can self-re...

ey0020.8-13 | New Mechanisms | ESPEYB20

8.13. Low-dose IL-2 reduces IL-21(+) T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

JY Zhang , F Hamey , D Trzupek , M Mickunas , M Lee , L Godfrey , JHM Yang , ML Pekalski , J Kennet , F Waldron-Lynch , ML Evans , TIM Tree , LS Wicker , JA Todd , RC Ferreira

Brief summary: This study used high-resolution single-cell multiomics and flow cytometry on blood samples from patients with type 1 diabetes (T1D) to examine the effects of low-dose recombinant IL-2 (iLD-IL-2). Administration of iLD-IL-2 expanded thymic-derived FOXP3+HELIOS+ Tregs and CD56bright NK cells, reduced frequency of IL-21-producing CD4+T cells, and induced long-lived anti-inflammatory transcriptional changes in all T and NK...

ey0016.7-10 | Environmental Factors and Puberty | ESPEYB16

7.10. Is there a causal relationship between obesity and puberty?

T Reinehr , CL Roth

To read the full abstract: Lancet Child Adolesc Health. 2019 Jan;3(1):44–54.This article reviews cross-sectional, longitudinal and intervention studies regarding the bidirectional relationship between obesity and puberty.An increasing prevalence of obesity amongst children and adolescents is reported globally. Epidemiological cross-sectional and...

ey0020.4-13 | Effects of Hormone Intervention on the Immune System | ESPEYB20

4.13. Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: a cross-sectional study

GA Robinson , J Peng , H Peckham , G Butler , I Pineda-Torra , C Ciurtin , EC Jury

Brief summary: This study further explores the sex differences in autoimmune regulation and the control of normal inflammatory responses, and also helps us understand why there are sex differences in the aetiology of autoimmune diseases such as systemic lupus erythematosus (SLE). It demonstrates the changes that occur in cisgender pubertal development on the T regulatory cell (Treg), B cell and monocyte population, and using samples from transgender adolescents undergoing GnRH...