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Disease severity in K/BxN serum transfer-induced arthritis is not affected by IL-33 deficiency.

Martin P, Talabot-Ayer D, Seemayer CA, Vigne S, Lamacchia C, Rodriguez E, Finckh A, Smith DE, Gabay C, Palmer G - Arthritis Res. Ther. (2013)

Bottom Line: Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor.Disease severity was monitored by clinical and histological scoring.This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work suggested implication of the IL-33/ST2 axis in the pathogenesis of human and mouse arthritis. Here, we directly investigated the role of endogenous IL-33 in K/BxN serum transfer-induced arthritis by using IL-33 knockout (KO) mice.

Methods: Arthritis was induced by injection of complete K/BxN serum or purified IgG. Disease severity was monitored by clinical and histological scoring.

Results: K/BxN serum transfer induced pronounced arthritis with similar incidence and severity in IL-33 KO and wild-type (WT) mice. In contrast, disease development was significantly reduced in ST2 KO mice. IL-33 expression in synovial tissue was comparable in arthritic WT and ST2 KO mice, and absent in IL-33 KO mice. Transfer of purified arthritogenic IgG instead of complete K/BxN serum also resulted in similar arthritis severity in IL-33 KO and WT mice, excluding a contribution of IL-33 contained in the serum of donor mice to explain this result. We investigated additional potential confounding factors, including purity of genetic background, but the mechanisms underlying reduced arthritis in ST2 KO mice remained unclear.

Conclusions: The data obtained with IL-33 KO mice indicate that endogenous IL-33 is not required for the development of joint inflammation in K/BxN serum transfer-induced arthritis. On the contrary, arthritis severity was reduced in ST2 KO mice. This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains.

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Severity of serum transfer-induced arthritis is reduced in ST2, but not in IL-33 KO mice. (A) Incidence of arthritis is shown for WT (n = 14, dashed line), IL-33 KO (n = 12, gray line), and ST2 KO (n = 10, black line) mice. Incidence was significantly retarded in ST2 KO, as compared to WT or IL-33 KO mice (P < 0.01, longitudinal model for binomial data). (B-C) Arthritis severity scores (B) and number of affected paws (C) are shown as the mean ± SEM for WT (dashed line), IL-33 KO (gray line), and ST2 KO (black line) mice. The evolution of severity scores (B; P = 0.001, mixed model for repeated measures) and final disease severity were significantly decreased in ST2 KO, as compared to WT (*P < 0.05) and IL-33 KO (&P < 0.05) mice. Evolution of the number of affected paws tended to be lower in ST2 KO, as compared to IL-33 KO and WT mice (P = 0.05, longitudinal model for ordinal data). (D) Clinical scores for inflammation of the right hind paw, which was processed for histological evaluation, and histological scores for inflammation, polymorphonulcear cell (PMN) infiltration, cartilage and bone erosion are shown as the mean ± SEM for WT (open columns), IL-33 KO (gray columns), and ST2 KO (black columns) mice. Cartilage and bone erosion were significantly reduced in ST2 KO, as compared to IL-33 KO mice; &P < 0.05. KO, knockout; WT, wild-type.
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Figure 1: Severity of serum transfer-induced arthritis is reduced in ST2, but not in IL-33 KO mice. (A) Incidence of arthritis is shown for WT (n = 14, dashed line), IL-33 KO (n = 12, gray line), and ST2 KO (n = 10, black line) mice. Incidence was significantly retarded in ST2 KO, as compared to WT or IL-33 KO mice (P < 0.01, longitudinal model for binomial data). (B-C) Arthritis severity scores (B) and number of affected paws (C) are shown as the mean ± SEM for WT (dashed line), IL-33 KO (gray line), and ST2 KO (black line) mice. The evolution of severity scores (B; P = 0.001, mixed model for repeated measures) and final disease severity were significantly decreased in ST2 KO, as compared to WT (*P < 0.05) and IL-33 KO (&P < 0.05) mice. Evolution of the number of affected paws tended to be lower in ST2 KO, as compared to IL-33 KO and WT mice (P = 0.05, longitudinal model for ordinal data). (D) Clinical scores for inflammation of the right hind paw, which was processed for histological evaluation, and histological scores for inflammation, polymorphonulcear cell (PMN) infiltration, cartilage and bone erosion are shown as the mean ± SEM for WT (open columns), IL-33 KO (gray columns), and ST2 KO (black columns) mice. Cartilage and bone erosion were significantly reduced in ST2 KO, as compared to IL-33 KO mice; &P < 0.05. KO, knockout; WT, wild-type.

Mentions: IL-33 KO, ST2 KO and WT mice (n = 3 per genotype) were randomly selected at the end of the experiment shown in Figure 1 and genotyped for 55 microsatellite markers as described [32]. In addition, all ST2 KO mice used in the arthritis experiments described herein were screened for D1Mit3, D1Mit211, D1Mit75a, D1Mit303, D6Mit166, D6Mit159, D6Mit102, and D15Mit193 genotypes using appropriate primers ([32]; see [33] for additional primer information).


Disease severity in K/BxN serum transfer-induced arthritis is not affected by IL-33 deficiency.

Martin P, Talabot-Ayer D, Seemayer CA, Vigne S, Lamacchia C, Rodriguez E, Finckh A, Smith DE, Gabay C, Palmer G - Arthritis Res. Ther. (2013)

Severity of serum transfer-induced arthritis is reduced in ST2, but not in IL-33 KO mice. (A) Incidence of arthritis is shown for WT (n = 14, dashed line), IL-33 KO (n = 12, gray line), and ST2 KO (n = 10, black line) mice. Incidence was significantly retarded in ST2 KO, as compared to WT or IL-33 KO mice (P < 0.01, longitudinal model for binomial data). (B-C) Arthritis severity scores (B) and number of affected paws (C) are shown as the mean ± SEM for WT (dashed line), IL-33 KO (gray line), and ST2 KO (black line) mice. The evolution of severity scores (B; P = 0.001, mixed model for repeated measures) and final disease severity were significantly decreased in ST2 KO, as compared to WT (*P < 0.05) and IL-33 KO (&P < 0.05) mice. Evolution of the number of affected paws tended to be lower in ST2 KO, as compared to IL-33 KO and WT mice (P = 0.05, longitudinal model for ordinal data). (D) Clinical scores for inflammation of the right hind paw, which was processed for histological evaluation, and histological scores for inflammation, polymorphonulcear cell (PMN) infiltration, cartilage and bone erosion are shown as the mean ± SEM for WT (open columns), IL-33 KO (gray columns), and ST2 KO (black columns) mice. Cartilage and bone erosion were significantly reduced in ST2 KO, as compared to IL-33 KO mice; &P < 0.05. KO, knockout; WT, wild-type.
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Figure 1: Severity of serum transfer-induced arthritis is reduced in ST2, but not in IL-33 KO mice. (A) Incidence of arthritis is shown for WT (n = 14, dashed line), IL-33 KO (n = 12, gray line), and ST2 KO (n = 10, black line) mice. Incidence was significantly retarded in ST2 KO, as compared to WT or IL-33 KO mice (P < 0.01, longitudinal model for binomial data). (B-C) Arthritis severity scores (B) and number of affected paws (C) are shown as the mean ± SEM for WT (dashed line), IL-33 KO (gray line), and ST2 KO (black line) mice. The evolution of severity scores (B; P = 0.001, mixed model for repeated measures) and final disease severity were significantly decreased in ST2 KO, as compared to WT (*P < 0.05) and IL-33 KO (&P < 0.05) mice. Evolution of the number of affected paws tended to be lower in ST2 KO, as compared to IL-33 KO and WT mice (P = 0.05, longitudinal model for ordinal data). (D) Clinical scores for inflammation of the right hind paw, which was processed for histological evaluation, and histological scores for inflammation, polymorphonulcear cell (PMN) infiltration, cartilage and bone erosion are shown as the mean ± SEM for WT (open columns), IL-33 KO (gray columns), and ST2 KO (black columns) mice. Cartilage and bone erosion were significantly reduced in ST2 KO, as compared to IL-33 KO mice; &P < 0.05. KO, knockout; WT, wild-type.
Mentions: IL-33 KO, ST2 KO and WT mice (n = 3 per genotype) were randomly selected at the end of the experiment shown in Figure 1 and genotyped for 55 microsatellite markers as described [32]. In addition, all ST2 KO mice used in the arthritis experiments described herein were screened for D1Mit3, D1Mit211, D1Mit75a, D1Mit303, D6Mit166, D6Mit159, D6Mit102, and D15Mit193 genotypes using appropriate primers ([32]; see [33] for additional primer information).

Bottom Line: Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor.Disease severity was monitored by clinical and histological scoring.This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work suggested implication of the IL-33/ST2 axis in the pathogenesis of human and mouse arthritis. Here, we directly investigated the role of endogenous IL-33 in K/BxN serum transfer-induced arthritis by using IL-33 knockout (KO) mice.

Methods: Arthritis was induced by injection of complete K/BxN serum or purified IgG. Disease severity was monitored by clinical and histological scoring.

Results: K/BxN serum transfer induced pronounced arthritis with similar incidence and severity in IL-33 KO and wild-type (WT) mice. In contrast, disease development was significantly reduced in ST2 KO mice. IL-33 expression in synovial tissue was comparable in arthritic WT and ST2 KO mice, and absent in IL-33 KO mice. Transfer of purified arthritogenic IgG instead of complete K/BxN serum also resulted in similar arthritis severity in IL-33 KO and WT mice, excluding a contribution of IL-33 contained in the serum of donor mice to explain this result. We investigated additional potential confounding factors, including purity of genetic background, but the mechanisms underlying reduced arthritis in ST2 KO mice remained unclear.

Conclusions: The data obtained with IL-33 KO mice indicate that endogenous IL-33 is not required for the development of joint inflammation in K/BxN serum transfer-induced arthritis. On the contrary, arthritis severity was reduced in ST2 KO mice. This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains.

Show MeSH
Related in: MedlinePlus