Limits...
Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of collagen-induced arthritis.

Yuan X, Garrett-Sinha LA, Sarkar D, Yang S - Bone Res (2014)

Bottom Line: Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro.However, how IFT20 regulates T-cell development and activation in vivo is still unknown.These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York , Buffalo, NY 14214, USA.

ABSTRACT
IFT20 is the smallest member of the intraflagellar transport protein (IFT) complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20(flox/flox) (IFT20(f/f) ) mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis (CIA). We found that both Lck-Cre/IFT20(f/f) and CD4-Cre/IFT20(f/f) mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20(f/f) mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20(f/f) mice compared to Lck-Cre/IFT20(+/+) littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20(f/f) mice had only mild effects on the development of T cells and CIA. The expression of IL-1β, IL-6 and TGF-β1 were significantly downregulated in the paw of Lck-Cre/IFT20(f/f) mice, but just slight decreased in CD4-Cre/IFT20(f/f) mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

No MeSH data available.


Related in: MedlinePlus

Deletion of IFT20 protected against histopathological progression of arthritis in Lck-Cre/IFT20f/f mice, but not in CD4-Cre/IFT20f/f mice. (a) Representative H&E-stained section of interphalangeal joints from Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice. Synovial hyperplasia and pannus formation were inhibited and destruction of articular cartilage was alleviated in Lck-Cre/IFT20f/f mice. Arrow indicates cartilage destruction; Δ indicates infiltration of inflammatory cells; * indicates fibrovascular synovial and periarticular proliferation. (b) The histopathological change was scored and data is expressed as mean ± S.D. for each group of 6 samples (n=6, P<0.01). (c) Indices of thymus and spleen in CIA in Lck-Cre/IFT20+/+ and Lck-Cre/ IFT20f/f mice (n=8). (d) Representative H&E-stained section of interphalangeal joints from CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice. (e) Histological scores of synovial inflammation and cartilage erosion was shown as mean±s.d. (n=6). (f) Indices of thymus and spleen in collagen-induced arthritis in CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=8). (g) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice (n=4, P<0.01). (h) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=4). ND indicated no significantly difference. H&E, hematoxylin and eosin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4470568&req=5

Figure 6: Deletion of IFT20 protected against histopathological progression of arthritis in Lck-Cre/IFT20f/f mice, but not in CD4-Cre/IFT20f/f mice. (a) Representative H&E-stained section of interphalangeal joints from Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice. Synovial hyperplasia and pannus formation were inhibited and destruction of articular cartilage was alleviated in Lck-Cre/IFT20f/f mice. Arrow indicates cartilage destruction; Δ indicates infiltration of inflammatory cells; * indicates fibrovascular synovial and periarticular proliferation. (b) The histopathological change was scored and data is expressed as mean ± S.D. for each group of 6 samples (n=6, P<0.01). (c) Indices of thymus and spleen in CIA in Lck-Cre/IFT20+/+ and Lck-Cre/ IFT20f/f mice (n=8). (d) Representative H&E-stained section of interphalangeal joints from CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice. (e) Histological scores of synovial inflammation and cartilage erosion was shown as mean±s.d. (n=6). (f) Indices of thymus and spleen in collagen-induced arthritis in CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=8). (g) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice (n=4, P<0.01). (h) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=4). ND indicated no significantly difference. H&E, hematoxylin and eosin.

Mentions: In the histological analysis, the affected joints of Lck-Cre/ IFT20+/+ mice and CD4-Cre/IFT20+/+ mice showed typical features of arthritis, characterized by synovial hyperplasia and perivascular infiltration of inflammatory cells. In severely affected joints, there was marked cartilage destruction (Figure 6a and 6d). However, the joints of Lck-Cre/IFT20f/f mice did not have any significant sign of tissue degeneration or inflammation. In contrast, both CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice showed a similar level of joint inflammation and articular cartilage degeneration (Figure 6d). Semiquantitative scoring of these histological parameters confirmed that arthritic severity in CD4-Cre/IFT20f/f was comparable to that of CD4-Cre/IFT20+/+ mice (Figure 6e), whereas Lck-Cre/ IFT20f/f mice were strongly protected against CIA histopathology (Figure 6b).


Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of collagen-induced arthritis.

Yuan X, Garrett-Sinha LA, Sarkar D, Yang S - Bone Res (2014)

Deletion of IFT20 protected against histopathological progression of arthritis in Lck-Cre/IFT20f/f mice, but not in CD4-Cre/IFT20f/f mice. (a) Representative H&E-stained section of interphalangeal joints from Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice. Synovial hyperplasia and pannus formation were inhibited and destruction of articular cartilage was alleviated in Lck-Cre/IFT20f/f mice. Arrow indicates cartilage destruction; Δ indicates infiltration of inflammatory cells; * indicates fibrovascular synovial and periarticular proliferation. (b) The histopathological change was scored and data is expressed as mean ± S.D. for each group of 6 samples (n=6, P<0.01). (c) Indices of thymus and spleen in CIA in Lck-Cre/IFT20+/+ and Lck-Cre/ IFT20f/f mice (n=8). (d) Representative H&E-stained section of interphalangeal joints from CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice. (e) Histological scores of synovial inflammation and cartilage erosion was shown as mean±s.d. (n=6). (f) Indices of thymus and spleen in collagen-induced arthritis in CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=8). (g) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice (n=4, P<0.01). (h) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=4). ND indicated no significantly difference. H&E, hematoxylin and eosin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470568&req=5

Figure 6: Deletion of IFT20 protected against histopathological progression of arthritis in Lck-Cre/IFT20f/f mice, but not in CD4-Cre/IFT20f/f mice. (a) Representative H&E-stained section of interphalangeal joints from Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice. Synovial hyperplasia and pannus formation were inhibited and destruction of articular cartilage was alleviated in Lck-Cre/IFT20f/f mice. Arrow indicates cartilage destruction; Δ indicates infiltration of inflammatory cells; * indicates fibrovascular synovial and periarticular proliferation. (b) The histopathological change was scored and data is expressed as mean ± S.D. for each group of 6 samples (n=6, P<0.01). (c) Indices of thymus and spleen in CIA in Lck-Cre/IFT20+/+ and Lck-Cre/ IFT20f/f mice (n=8). (d) Representative H&E-stained section of interphalangeal joints from CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice. (e) Histological scores of synovial inflammation and cartilage erosion was shown as mean±s.d. (n=6). (f) Indices of thymus and spleen in collagen-induced arthritis in CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=8). (g) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of Lck-Cre/IFT20+/+ and Lck-Cre/IFT20f/f mice (n=4, P<0.01). (h) Comparison of IL-1, IL-6 and TGF-β1 mRNA levels in the hind paws of CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice (n=4). ND indicated no significantly difference. H&E, hematoxylin and eosin.
Mentions: In the histological analysis, the affected joints of Lck-Cre/ IFT20+/+ mice and CD4-Cre/IFT20+/+ mice showed typical features of arthritis, characterized by synovial hyperplasia and perivascular infiltration of inflammatory cells. In severely affected joints, there was marked cartilage destruction (Figure 6a and 6d). However, the joints of Lck-Cre/IFT20f/f mice did not have any significant sign of tissue degeneration or inflammation. In contrast, both CD4-Cre/IFT20+/+ and CD4-Cre/IFT20f/f mice showed a similar level of joint inflammation and articular cartilage degeneration (Figure 6d). Semiquantitative scoring of these histological parameters confirmed that arthritic severity in CD4-Cre/IFT20f/f was comparable to that of CD4-Cre/IFT20+/+ mice (Figure 6e), whereas Lck-Cre/ IFT20f/f mice were strongly protected against CIA histopathology (Figure 6b).

Bottom Line: Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro.However, how IFT20 regulates T-cell development and activation in vivo is still unknown.These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York , Buffalo, NY 14214, USA.

ABSTRACT
IFT20 is the smallest member of the intraflagellar transport protein (IFT) complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20(flox/flox) (IFT20(f/f) ) mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis (CIA). We found that both Lck-Cre/IFT20(f/f) and CD4-Cre/IFT20(f/f) mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20(f/f) mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20(f/f) mice compared to Lck-Cre/IFT20(+/+) littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20(f/f) mice had only mild effects on the development of T cells and CIA. The expression of IL-1β, IL-6 and TGF-β1 were significantly downregulated in the paw of Lck-Cre/IFT20(f/f) mice, but just slight decreased in CD4-Cre/IFT20(f/f) mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

No MeSH data available.


Related in: MedlinePlus