Ajatus tänään: Miten exokriininen pancreassolu voi?

Voisiko betasolut sairastua exokriinisen haiman takia (=sekundaaristi)?

Katson hakusanalla Exocrine pancreas cell. Katson ensin mämä kolem artikkeliä mennävuosilta

1. Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes. Rodriguez-Calvo T et al. Diabetes. (2014)

 

2. Regeneration and repair of the exocrine pancreas. Murtaugh LC et al. Annu Rev Physiol. (2015)

 

3. Abnormalities of the Exocrine Pancreas in Type 1 Diabetes. Campbell-Thompson M et al. Curr Diab Rep. (2015)

• 1. artikkeli ja sen kommentti

Diabetes. 2014 Nov;63(11):3880-90. doi: 10.2337/db14-0549. Epub 2014 Jun 19.

Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes.

Rodriguez-Calvo T¹, Ekwall O², Amirian N¹, Zapardiel-Gonzalo J³, von Herrath MG⁴.

Erratum in

• Erratum. Increased Immune Cell Infiltration of the Exocrine Pancreas: A Possible Contribution to the Pathogenesis of Type 1 Diabetes. Diabetes 2014;63:3880-3890. [Diabetes. 2016]

1-tyypin  diabetes (T1D) johtuu monimutkaisesta  keskinäisestä vuorovaikutukseta    geneettisen alttiuden ja sellaisten miljöötekijöiden kesken, joita on  pidetty taudin patogeneesissa  sekä  betasolu tuhon liipaisijana että vahvistajina.

• Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors that have been implicated in the pathogenesis of disease both as triggers and potentiators of β-cell destruction. 

 Tappaja-T-solut eli CD8T-solut  ovat päätyyppi imusoluja ihmisen betasolusaarekkeessa ja niiden on  osoitettu koeputkessa  voivan  tappaa sellaisia beta-soluja, jotka ilmentävät ylimäärin MHC I-luokan modulia.

• CD8 T cells are the main cell type found in human islets, and they have been shown in vitro to be capable of killing β-cells overexpressing MHC class I. 

 Tässä artikkelin tutkimuksessa  raportoidaan CD8 T-solu infiltraateista  exokriinisssä haimassa diabeettisilla henkilöiollä suurin määrin- eikä vain  betasolusaarekkeissa! T1D- henkilöillä esiintyy   CD8 T-solujen  merkitsevän korkeaa tiheyttä  exokriinisessa haimassa ilman,  että on  havaittavaa insuliittia .
Myös  TiD donoreilla, joilla ei ole jäljellä insuliinia sisältäviä saarekkeita ja pitkää  sairashistoriaa, näyttävät omaavan  exokriinisessä haima-aitiossa  kohonneet pitoisuudet CD8 T-soluja. Mainittujen solujen lisäksi on havaittu CD4(+) ja CD11c(+) soluja exokriinisessa haimassa.

• In this study, we report that CD8 T cells infiltrate the exocrine pancreas of diabetic subjects in high numbers and not only endocrine areas. T1D subjects present significantly higher CD8 T cell density in the exocrine tissue without the presence of prominent insulitis. Even T1D donors without remaining insulin-containing islets and long disease duration show elevated levels of CD8 T cells in the exocrine compartment. In addition, higher numbers of CD4(+) and CD11c(+) cells were found in the exocrine tissue. 

Preliminäärinen tieto T2D- henkilöiltä viitaa siihen, että kaikkialla exokriinisessä haimassa  saattaisi olla spontaaneja tulehduksellisia  infiltraatteja, jotka ovat tyypillisiä sekä T1D että T2D-henkilöille.  Tämä tutkimus antaa ensimmäistä kertaa tietoa haiman CD8 T-solujen  tarkasta kudosjakaumasta T1D ja T2D:ssa, autovasta-ainepositiivisilla  sekä terveillä kontrolleilla.

• Preliminary data in type 2 diabetic (T2D) subjects indicate that overall, there might be a spontaneous inflammatory infiltration of the exocrine tissue, common to both T1D and T2D subjects. Our study provides the first information on the precise tissue distribution of CD8 T cells in pancreata from T1D, T2D, autoantibody-positive, and healthy control subjects.

Comment in

• Losing a grip on the notion of β-cell specificity for immune responses in type 1 diabetes: can we handle the truth? [Diabetes. 2014]

[Indexed for MEDLINE]
Studies—some decades old—have noted a variety of unusual physiologic and pathologic features associated with the pancreas in T1D (Fig. 1). These include a propensity for exocrine insufficiency, exocrine atrophy, and other tissue-related abnormalities including fibrosis (10–12). The pancreas in T1D also is the target of a series of immunological aberrations, including autoantibodies targeting exocrine constituents, deposition of the complement degradation product C4d, and neutrophil infiltration of the pancreatic parenchyma (13–15). Beyond these, a variety of techniques and tissue sources (e.g., autopsy, organ donors) have led investigations to suggest pancreatic weights and volumes are reduced by 20–50% in T1D patients when compared with control subjects of similar age (16). Free PMC Article

• 2. artikkeli

Annu Rev Physiol. 2015;77:229-49. doi: 10.1146/annurev-physiol-021014-071727. Epub 2014 Oct 24.

Regeneration and repair of the exocrine pancreas.

Murtaugh LC¹, Keefe MD.

Pancreatitis is caused by inflammatory injury to the exocrine pancreas, from which both humans and animal models appear to recover via regeneration of digestive enzyme-producing acinar cells. This regenerative process involves transient phases of inflammation, metaplasia, and redifferentiation, driven by cell-cell interactions between acinar cells, leukocytes, and resident fibroblasts. The NFκB signaling pathway is a critical determinant of pancreatic inflammation and metaplasia, whereas a number of developmental signals and transcription factors are devoted to promoting acinar redifferentiation after injury. Imbalances between these proinflammatory and prodifferentiation pathways contribute to chronic pancreatitis, characterized by persistent inflammation, fibrosis, and acinar dedifferentiation. Loss of acinar cell differentiation also drives pancreatic cancer initiation, providing a mechanistic link between pancreatitis and cancer risk. Unraveling the molecular bases of exocrine regeneration may identify new therapeutic targets for treatment and prevention of both of these deadly diseases.

KEYWORDS:
acinar cell; caerulein; cerulein; differentiation; inflammation; metaplasia; pancreatitis

• 3. artikkeli

  Curr Diab Rep. 2015 Oct;15(10):79. doi: 10.1007/s11892-015-0653-y.
  Abnormalities of the Exocrine Pancreas in Type 1 Diabetes.
  Campbell-Thompson M¹, Rodriguez-Calvo T, Battaglia M.
  Type 1 diabetes (T1D) is considered a pancreatic beta cell-specific disease that results in absolute insulin deficiency. Nevertheless, clinical studies from 1940 onwards showed that patients with T1D had an abnormal exocrine pancreas due to the presence of subclinical exocrine insufficiency and acinar atrophy. Exocrine abnormalities are an important, and mostly neglected, characteristic associated with T1D. It is however still unclear whether the exocrine dysfunction in T1D is a primary damage caused by the same pathogenic event that led to beta cell destruction or secondary to beta cell loss. In this review, we collect evidence supporting the hypothesis that T1D is a combined endocrine-exocrine disease in which the loss of functional beta cell mass is most clinically apparent.

  PMID:

  26318606

  PMCID:

  PMC5072278

  DOI:

  10.1007/s11892-015-0653-y

  [Indexed for MEDLINE]

  Free PMC Article