Functional significance of MAIT cells in psoriatic arthritis

Smriti K. Raychaudhuri, Christine Abria, Anupam Mitra, Siba P Raychaudhuri

Research output: Contribution to journalArticle

Abstract

Background: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. Methods: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 for each) PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA). Hi-D FACS studies were performed: (i) activated memory cells (CD3+CD45RO+) T cells were identified (ii) gating strategies were made to identity the MAIT (CD3+Vα7.2TCR+CD161hi) cells, its phenotype pattern; and functional significance in respect to IL-17A production and responsiveness to human rIL-23. Anti CD3/CD28 ab cocktail was used to activate cells along with rIL-23 to culture and enrich the MAIT cells. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using Flow Jo software. Results: MAIT cells were enriched in synovial fluid of PsA (4.29 ± 0.82%) compared to PBMC (1.04 ± 0.71). With stimulation, SFMC MAIT cells produced significantly more IL-17A (32.66 ± 4.01%) compared to that of RA (23.93 ± 2.81%, p < 0.05) and OA (5.02 ± 0.16%, p < 0.05). MAIT cells were predominantly CD8+ (>80%). Significant upregulation of IL-23R was noted in synovial fluid MAIT cells of PsA (24.97 ± 2.33%, p < 0.001) and RA (21.93 ± 2.29%, p < 0.001) compared to that of OA (2.13 ± 2.29). This IL-23R was functionally active as evidenced by profound mitotic effect in presence of rIL-23. Conclusion: MAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-γ, TNF-α). Here, we demonstrated synovial fluid MAIT cells as a major source of IL-17A and majority of MAIT cells were CD8+. Functionally active IL-23R on these migrated MAIT cells brings a new dimension. They may not need MR1 associated activation rather lesional IL-23 in the synovium can independently regulate these critical Tc17 CD8+ MAIT cells. Thus, these cells likely to be a part of the IL-23/IL-17A cytokine network and play a critical role in the pathogenesis of PsA.

Original languageEnglish (US)
Article number154855
JournalCytokine
Volume125
DOIs
StatePublished - Jan 1 2020

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Psoriatic Arthritis
T-cells
Interleukin-17
Synovial Fluid
Fluids
Interleukin-23
Rheumatoid Arthritis
Osteoarthritis
Mucosal-Associated Invariant T Cells
Blood Cells
Blood
Cytokines
Synovial Membrane
Adaptive Immunity
Innate Immunity
Autoimmune Diseases
Cell culture
Up-Regulation
Software
Fluorescence

Keywords

  • IL-17A
  • IL-23R
  • MAIT cells
  • Psoriatic arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Functional significance of MAIT cells in psoriatic arthritis. / Raychaudhuri, Smriti K.; Abria, Christine; Mitra, Anupam; Raychaudhuri, Siba P.

In: Cytokine, Vol. 125, 154855, 01.01.2020.

Research output: Contribution to journalArticle

Raychaudhuri, Smriti K. ; Abria, Christine ; Mitra, Anupam ; Raychaudhuri, Siba P. / Functional significance of MAIT cells in psoriatic arthritis. In: Cytokine. 2020 ; Vol. 125.
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title = "Functional significance of MAIT cells in psoriatic arthritis",
abstract = "Background: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. Methods: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 for each) PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA). Hi-D FACS studies were performed: (i) activated memory cells (CD3+CD45RO+) T cells were identified (ii) gating strategies were made to identity the MAIT (CD3+Vα7.2TCR+CD161hi) cells, its phenotype pattern; and functional significance in respect to IL-17A production and responsiveness to human rIL-23. Anti CD3/CD28 ab cocktail was used to activate cells along with rIL-23 to culture and enrich the MAIT cells. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using Flow Jo software. Results: MAIT cells were enriched in synovial fluid of PsA (4.29 ± 0.82{\%}) compared to PBMC (1.04 ± 0.71). With stimulation, SFMC MAIT cells produced significantly more IL-17A (32.66 ± 4.01{\%}) compared to that of RA (23.93 ± 2.81{\%}, p < 0.05) and OA (5.02 ± 0.16{\%}, p < 0.05). MAIT cells were predominantly CD8+ (>80{\%}). Significant upregulation of IL-23R was noted in synovial fluid MAIT cells of PsA (24.97 ± 2.33{\%}, p < 0.001) and RA (21.93 ± 2.29{\%}, p < 0.001) compared to that of OA (2.13 ± 2.29). This IL-23R was functionally active as evidenced by profound mitotic effect in presence of rIL-23. Conclusion: MAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-γ, TNF-α). Here, we demonstrated synovial fluid MAIT cells as a major source of IL-17A and majority of MAIT cells were CD8+. Functionally active IL-23R on these migrated MAIT cells brings a new dimension. They may not need MR1 associated activation rather lesional IL-23 in the synovium can independently regulate these critical Tc17 CD8+ MAIT cells. Thus, these cells likely to be a part of the IL-23/IL-17A cytokine network and play a critical role in the pathogenesis of PsA.",
keywords = "IL-17A, IL-23R, MAIT cells, Psoriatic arthritis",
author = "Raychaudhuri, {Smriti K.} and Christine Abria and Anupam Mitra and Raychaudhuri, {Siba P}",
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T1 - Functional significance of MAIT cells in psoriatic arthritis

AU - Raychaudhuri, Smriti K.

AU - Abria, Christine

AU - Mitra, Anupam

AU - Raychaudhuri, Siba P

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. Methods: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 for each) PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA). Hi-D FACS studies were performed: (i) activated memory cells (CD3+CD45RO+) T cells were identified (ii) gating strategies were made to identity the MAIT (CD3+Vα7.2TCR+CD161hi) cells, its phenotype pattern; and functional significance in respect to IL-17A production and responsiveness to human rIL-23. Anti CD3/CD28 ab cocktail was used to activate cells along with rIL-23 to culture and enrich the MAIT cells. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using Flow Jo software. Results: MAIT cells were enriched in synovial fluid of PsA (4.29 ± 0.82%) compared to PBMC (1.04 ± 0.71). With stimulation, SFMC MAIT cells produced significantly more IL-17A (32.66 ± 4.01%) compared to that of RA (23.93 ± 2.81%, p < 0.05) and OA (5.02 ± 0.16%, p < 0.05). MAIT cells were predominantly CD8+ (>80%). Significant upregulation of IL-23R was noted in synovial fluid MAIT cells of PsA (24.97 ± 2.33%, p < 0.001) and RA (21.93 ± 2.29%, p < 0.001) compared to that of OA (2.13 ± 2.29). This IL-23R was functionally active as evidenced by profound mitotic effect in presence of rIL-23. Conclusion: MAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-γ, TNF-α). Here, we demonstrated synovial fluid MAIT cells as a major source of IL-17A and majority of MAIT cells were CD8+. Functionally active IL-23R on these migrated MAIT cells brings a new dimension. They may not need MR1 associated activation rather lesional IL-23 in the synovium can independently regulate these critical Tc17 CD8+ MAIT cells. Thus, these cells likely to be a part of the IL-23/IL-17A cytokine network and play a critical role in the pathogenesis of PsA.

AB - Background: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. Methods: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 for each) PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA). Hi-D FACS studies were performed: (i) activated memory cells (CD3+CD45RO+) T cells were identified (ii) gating strategies were made to identity the MAIT (CD3+Vα7.2TCR+CD161hi) cells, its phenotype pattern; and functional significance in respect to IL-17A production and responsiveness to human rIL-23. Anti CD3/CD28 ab cocktail was used to activate cells along with rIL-23 to culture and enrich the MAIT cells. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using Flow Jo software. Results: MAIT cells were enriched in synovial fluid of PsA (4.29 ± 0.82%) compared to PBMC (1.04 ± 0.71). With stimulation, SFMC MAIT cells produced significantly more IL-17A (32.66 ± 4.01%) compared to that of RA (23.93 ± 2.81%, p < 0.05) and OA (5.02 ± 0.16%, p < 0.05). MAIT cells were predominantly CD8+ (>80%). Significant upregulation of IL-23R was noted in synovial fluid MAIT cells of PsA (24.97 ± 2.33%, p < 0.001) and RA (21.93 ± 2.29%, p < 0.001) compared to that of OA (2.13 ± 2.29). This IL-23R was functionally active as evidenced by profound mitotic effect in presence of rIL-23. Conclusion: MAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-γ, TNF-α). Here, we demonstrated synovial fluid MAIT cells as a major source of IL-17A and majority of MAIT cells were CD8+. Functionally active IL-23R on these migrated MAIT cells brings a new dimension. They may not need MR1 associated activation rather lesional IL-23 in the synovium can independently regulate these critical Tc17 CD8+ MAIT cells. Thus, these cells likely to be a part of the IL-23/IL-17A cytokine network and play a critical role in the pathogenesis of PsA.

KW - IL-17A

KW - IL-23R

KW - MAIT cells

KW - Psoriatic arthritis

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