PMID- 33526907
OWN - NLM
STAT- MEDLINE
DCOM- 20210422
LR  - 20230129
IS  - 1759-5037 (Electronic)
IS  - 1759-5029 (Print)
IS  - 1759-5029 (Linking)
VI  - 17
IP  - 4
DP  - 2021 Apr
TI  - Immune dysfunction in developmental programming of type 2 diabetes mellitus.
PG  - 235-245
LID - 10.1038/s41574-020-00464-z [doi]
AB  - Intrauterine growth restriction (IUGR) is a common complication of pregnancy and 
      increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) 
      later in life. Alterations in the immune system are implicated in the 
      pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is 
      a delicate balance as it must remain tolerant of maternal antigens whilst also 
      preparing for the post-birth environment. In addition, the fetal immune system is 
      susceptible to an altered intrauterine milieu caused by maternal and placental 
      inflammatory mediators or secondary to nutrient and oxygen deprivation. 
      Pancreatic-resident macrophages populate the pancreas during fetal development, 
      and their phenotype is dynamic through the neonatal period. Furthermore, 
      macrophages in the islets are instrumental in islet development as they influence 
      beta-cell proliferation and islet neogenesis. In addition, cytokines, derived from 
      beta-cells and macrophages, are important to islet homeostasis in the fetus and 
      adult and, when perturbed, can cause islet dysfunction. Several activated immune 
      pathways have been identified in the islets of people who experienced IUGR, with 
      alternations in the levels of IL-1beta and IL-4 as well as changes in TGFbeta 
      signalling. Leptin levels are also altered. Immunomodulation has shown 
      therapeutic benefit in T2DM and might be particularly useful in IUGR-induced 
      T2DM.
FAU - Golden, Thea N
AU  - Golden TN
AD  - Center for Research on Reproduction and Women's Health, Perelman School of 
      Medicine University of Pennsylvania, Philadelphia, PA, USA.
AD  - Center of Excellence in Environmental Toxicology, Perelman School of Medicine 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Simmons, Rebecca A
AU  - Simmons RA
AD  - Center for Research on Reproduction and Women's Health, Perelman School of 
      Medicine University of Pennsylvania, Philadelphia, PA, USA. 
      rsimmons@pennmedicine.upenn.edu.
AD  - Center of Excellence in Environmental Toxicology, Perelman School of Medicine 
      University of Pennsylvania, Philadelphia, PA, USA. 
      rsimmons@pennmedicine.upenn.edu.
AD  - Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA. rsimmons@pennmedicine.upenn.edu.
LA  - eng
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 DK055704/DK/NIDDK NIH HHS/United States
GR  - R01 DK114054/DK/NIDDK NIH HHS/United States
GR  - T32 ES019851/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20210201
PL  - England
TA  - Nat Rev Endocrinol
JT  - Nature reviews. Endocrinology
JID - 101500078
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*etiology/*immunology
MH  - Fetal Development/*immunology
MH  - Fetal Growth Retardation/*immunology
MH  - Humans
MH  - Immune System/immunology
MH  - Prenatal Injuries/immunology
PMC - PMC7969450
MID - NIHMS1670872
EDAT- 2021/02/03 06:00
MHDA- 2021/04/23 06:00
PMCR- 2021/04/01
CRDT- 2021/02/02 06:08
PHST- 2020/12/17 00:00 [accepted]
PHST- 2021/02/03 06:00 [pubmed]
PHST- 2021/04/23 06:00 [medline]
PHST- 2021/02/02 06:08 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - 10.1038/s41574-020-00464-z [pii]
AID - 10.1038/s41574-020-00464-z [doi]
PST - ppublish
SO  - Nat Rev Endocrinol. 2021 Apr;17(4):235-245. doi: 10.1038/s41574-020-00464-z. Epub 
      2021 Feb 1.