2. Academic Validation
  3. CD4+IL9+ (Th9) cells as the major source of IL-9, potentially modulate Th17/Treg mediated host immune response during experimental cerebral malaria

CD4+IL9+ (Th9) cells as the major source of IL-9, potentially modulate Th17/Treg mediated host immune response during experimental cerebral malaria

  • Mol Immunol. 2022 Dec:152:240-254. doi: 10.1016/j.molimm.2022.11.005.
Soubhik Ghosh 1,  Saikat Mukherjee 2,  Anirban Sengupta 3,  Sreyoshi Chowdhury 4,  Samrat Sarkar 5,  Tarun Keswani 6,  Arindam Bhattacharyya 7
Affiliations

Affiliations

  • 1 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: soubhik1992@gmail.com.
  • 2 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: mukherjee.saikat053@gmail.com.
  • 3 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: online.asg@gmail.com.
  • 4 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: sreyoshi2013@gmail.com.
  • 5 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: ssarkar887@gmail.com.
  • 6 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: keswani22@gmail.com.
  • 7 Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: arindam19@yahoo.com.
PMID: 36395532 DOI: 10.1016/j.molimm.2022.11.005
Abstract

Th9, a new subgroup of CD4+T cells is characterized by its specific cytokine IL-9, is a critical factor in allergic diseases, cancers and parasitic infections. This study aimed to explore the potential roles of Th9 cells in the immunopathogenesis of ECM. In splenocytes sourced from uninfected, PbA and Py infected mice, Th9 cells were characterised by flow cytometry, cell sorting and qPCR. Enhancement of CD4+IL-9+ (Th9) cells were observed in both the infections, which corroborated with increased expression of the differentiating transcription factors. Moreover, crucial Cytokine Receptors (IL-4R, TGF-βR, IL-6R) as well as chemokine receptors (CCR3, CCR6 and CCR7) and activation marker (CD96), demonstrated elevation upon PbA Infection in splenic Th9 cells. Furthermore, Neutralization of IL-9 along with IL-6 enhanced host survivability, reduced mean neurological score of ECM. However, anti- IL-9 treatment also down regulated frequency of Th17 cells, and its transcription factors pSTAT3, RORγT along with depleted Il-1β and IL-6 expression. In sum, understanding how IL-9 producing CD4+ T-cells can alter Th17/Treg ratio and by that modulate host's immune response, could pave the way for developing immunomodulatory interventions against cerebral malaria.

Keywords

IL-9; Immune balance modulation and immunopathological severity; Malaria infection; Plasmodium berghei ANKA (PbA); Th17/Treg ratio; Th9.

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