Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 29;12(11):1495.
doi: 10.3390/cells12111495.

The Emerging Roles of the Adaptive Immune Response in Acute Pancreatitis

Bojan Stojanovic  1 , Ivan P Jovanovic  2 , Milica Dimitrijevic Stojanovic  3 , Marina Jovanovic  4 , Berislav Vekic  1 , Bojan Milosevic  1 , Aleksandar Cvetkovic  1 , Marko Spasic  1 , Bojana S Stojanovic  5
Affiliations
Review

The Emerging Roles of the Adaptive Immune Response in Acute Pancreatitis

Bojan Stojanovic et al. Cells. .

Abstract

Acute pancreatitis (AP) is an abrupt, variable inflammatory condition of the pancreas, potentially escalating to severe systemic inflammation, rampant pancreatic necrosis, and multi-organ failure. Its complex pathogenesis involves an intricate immune response, with different T cell subsets (Th1, Th2, Th9, Th17, Th22, TFH, Treg, and CD8+ T cells) and B cells playing pivotal roles. Early T cell activation initiates the AP development, triggering cytokines associated with the Th1 response, which stimulate macrophages and neutrophils. Other T cell phenotypes contribute to AP's pathogenesis, and the balance between pro-inflammatory and anti-inflammatory cytokines influences its progression. Regulatory T and B cells are crucial for moderating the inflammatory response and promoting immune tolerance. B cells further contribute through antibody production, antigen presentation, and cytokine secretion. Understanding these immune cells' roles in AP could aid in developing new immunotherapies to enhance patient outcomes. However, further research is required to define these cells' precise roles in AP and their potential as therapeutic targets.

Keywords: B cells; T cells; acute pancreatitis; immune response.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interest or conflict of interest with regard to the research, authorship, and publication of this study.

Figures

Figure 1
Figure 1
Mechanisms of T Lymphocyte Depletion and Pancreatic Damage in Acute Pancreatitis. This figure illustrates the depletion of circulating T lymphocytes in acute pancreatitis development due to the following two primary factors: increased apoptosis of T lymphocytes caused by heightened Fas/FasL signaling pathway and caspase activation, and enhanced T cell homing to inflamed tissues through rolling, chemokine-mediated activation, and firm adhesion. As a result, the inflamed pancreas experiences increased T cells that directly and indirectly damage the pancreatic parenchyma, with direct damage mediated by CD8+ T cells and FasL/Fas interactions, and indirect damage mediated by Th1 and Th17 cells that stimulate macrophage activation and neutrophil influx, respectively.
Figure 2
Figure 2
Adaptive Immune Response in Severe Acute Pancreatitis (SAP). The figure details the dynamic immune landscape during SAP, highlighting the decrease in T and helper T cells, increase in cytotoxic T and Th17 cells, and the shift from initial Th2 to later Th1 dominance. It underscores the role of Th1-derived cytokines (IFN-γ, IL-6, TNF-α) in activating pro-inflammatory innate cells, and the contribution of IL-17 in neutrophil recruitment. Furthermore, it illustrates the rise in IL-21 (a TFH cell marker) and the compensatory activation of Tregs, predisposing to CARS. B cell responses are marked by increased numbers but suppressed functions, alongside a decrease in regulatory B cells. These changes characterize SAP, facilitating local complications of acute pancreatitis such as hemorrhage and pancreatic necrosis, and systemic complications such as acute respiratory distress syndrome.
Figure 3
Figure 3
Immune Landscape in Mild Acute Pancreatitis (MAP). The figure succinctly captures the anti-inflammatory shift in MAP, marked by decreased T and Th cell counts, and an increase in Th2 cells with enhanced IL-4 and IL-13 secretion, favoring M2 macrophage polarization. It spotlights the protective role of Th22 cells and the increased activation of Tregs in mitigating inflammatory damage. Additionally, it notes the rise of cytotoxic T cells exhibiting anti-inflammatory phenotypes and B cells with a predominant immunomodulatory role, inhibiting Th1 and Th17 responses. These dynamics collectively characterize the mild AP course.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Walkowska J., Zielinska N., Tubbs R.S., Podgórski M., Dłubek-Ruxer J., Olewnik Ł. Diagnosis and Treatment of Acute Pancreatitis. Diagnostics. 2022;12:1974. doi: 10.3390/diagnostics12081974. - DOI - PMC - PubMed
    1. Song T.-J., Ke J., Chen F., Zhang J.-Y., Zhang C., Chen H.-Y. Effect of SNHG11/miR-7-5p/PLCB1 Axis on Acute Pancreatitis through Inhibiting p38MAPK Pathway. Cells. 2023;12:65. doi: 10.3390/cells12010065. - DOI - PMC - PubMed
    1. Klöppel G. Acute pancreatitis. Semin. Diagn. Pathol. 2004;21:221–226. doi: 10.1053/j.semdp.2005.07.001. - DOI - PubMed
    1. Leonard-Murali S., Lezotte J., Kalu R., Blyden D.J., Patton J.H., Johnson J.L., Gupta A.H. Necrotizing Pancreatitis: A Review for the Acute Care Surgeon. Am. J. Surg. 2021;221:927–934. doi: 10.1016/j.amjsurg.2020.08.027. - DOI - PMC - PubMed
    1. Garg P.K., Singh V.P. Organ Failure Due to Systemic Injury in Acute Pancreatitis. Gastroenterology. 2019;156:2008–2023. doi: 10.1053/j.gastro.2018.12.041. - DOI - PMC - PubMed

Publication types

Grants and funding

This research was funded by the Ministry of Science, Technological Development, and Innovation of the Republic of Serbia, contract number for 2023: 451-03-47/2023-01/200111, and the Faculty of Medical Sciences of the University of Kragujevac, Serbia (JP11/18).